{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:38:46Z","timestamp":1790127526477,"version":"4.0.1"},"reference-count":130,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Iowa State University College of Veterinary Medicine"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vector-borne, filarial nematode diseases cause significant disease burdens in humans and domestic animals worldwide. Although there is strong direct evidence of parasite-driven immunomodulation of mammalian host responses, there is less evidence of parasite immunomodulation of the vector host. We have previously reported that all life stages of <jats:italic>Brugia malayi<\/jats:italic>, a filarial nematode and causative agent of Lymphatic filariasis, secrete extracellular vesicles (EVs). Here we investigate the immunomodulatory effects of microfilariae-derived EVs on the vector host <jats:italic>Aedes aegypti.<\/jats:italic> RNA-seq analysis of an <jats:italic>Ae. aegypti<\/jats:italic> cell line treated with <jats:italic>B. malayi<\/jats:italic> microfilariae EVs showed differential expression of both mRNAs and miRNAs. AAEL002590, an <jats:italic>Ae. aegypti<\/jats:italic> gene encoding a serine protease, was shown to be downregulated when cells were treated with biologically relevant EV concentrations in vitro. Injection of adult female mosquitoes with biologically relevant concentrations of EVs validated these results in vivo, recapitulating the downregulation of AAEL002590 transcript. This gene was predicted to be involved in the mosquito phenoloxidase (PO) cascade leading to the canonical melanization response and correspondingly, both suppression of this gene using RNAi and parasite EV treatment reduced PO activity in vivo. Our data indicate that parasite-derived EVs interfere with critical immune responses in the vector host, including melanization.<\/jats:p>","DOI":"10.1038\/s41598-023-35940-9","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T10:02:24Z","timestamp":1685527344000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Extracellular vesicles secreted by Brugia malayi microfilariae modulate the melanization pathway in the mosquito host"],"prefix":"10.1038","volume":"13","author":[{"given":"Hannah J.","family":"Loghry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeogsun","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelle A.","family":"Sondjaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Minkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas J.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Zamanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyric C.","family":"Bartholomay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Kimber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"35940_CR1","unstructured":"World Health Organization. Global programme to eliminate lymphatic filariasis: Progress report, 2020 (2021). Accessed: Feb. 22, 2022. [Online]. https:\/\/www.who.int\/publications-detail-redirect\/who-wer9641-497-508"},{"key":"35940_CR2","unstructured":"WHO. Lymphatic filariasis. World Health Organization. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/lymphatic-filariasis (2022)."},{"issue":"12","key":"35940_CR3","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.pt.2011.09.001","volume":"27","author":"JC Castillo","year":"2011","unstructured":"Castillo, J. C., Reynolds, S. E. & Eleftherianos, I. Insect immune responses to nematode parasites. Trends Parasitol. 27(12), 537\u2013547. https:\/\/doi.org\/10.1016\/j.pt.2011.09.001 (2011).","journal-title":"Trends Parasitol."},{"key":"35940_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2020.01174","volume":"11","author":"Y Yang","year":"2022","unstructured":"Yang, Y. et al. Extracellular vesicles derived from Trichinella spiralis muscle larvae ameliorate TNBS-induced colitis in mice. Front. Immunol. 11, 1. https:\/\/doi.org\/10.3389\/fimmu.2020.01174 (2022).","journal-title":"Front. Immunol."},{"issue":"1","key":"35940_CR5","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/imr.12164","volume":"259","author":"CM Finlay","year":"2014","unstructured":"Finlay, C. M., Walsh, K. P. & Mills, K. H. G. Induction of regulatory cells by helminth parasites: Exploitation for the treatment of inflammatory diseases. Immunol. Rev. 259(1), 206\u2013230. https:\/\/doi.org\/10.1111\/imr.12164 (2014).","journal-title":"Immunol. Rev."},{"issue":"8","key":"35940_CR6","doi-asserted-by":"publisher","first-page":"4924","DOI":"10.4049\/jimmunol.174.8.4924","volume":"174","author":"MD Taylor","year":"2005","unstructured":"Taylor, M. D. et al. Removal of regulatory T cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo. J. Immunol. 174(8), 4924\u20134933. https:\/\/doi.org\/10.4049\/jimmunol.174.8.4924 (2005).","journal-title":"J. Immunol."},{"issue":"1","key":"35940_CR7","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1002\/eji.200838727","volume":"39","author":"MD Taylor","year":"2009","unstructured":"Taylor, M. D. et al. Early recruitment of natural CD4+Foxp3+ Treg cells by infective larvae determines the outcome of filarial infection. Eur. J. Immunol. 39(1), 192\u2013206. https:\/\/doi.org\/10.1002\/eji.200838727 (2009).","journal-title":"Eur. J. Immunol."},{"issue":"1","key":"35940_CR8","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1017\/S0031182010000922","volume":"138","author":"S Korten","year":"2011","unstructured":"Korten, S., Hoerauf, A., Kaifi, J. T. & B\u00fcttner, D. W. Low levels of transforming growth factor-beta (TGF-beta) and reduced suppression of Th2-mediated inflammation in hyperreactive human onchocerciasis. Parasitology 138(1), 35\u201345. https:\/\/doi.org\/10.1017\/S0031182010000922 (2011).","journal-title":"Parasitology"},{"issue":"4","key":"35940_CR9","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.4049\/jimmunol.0802767","volume":"182","author":"R D\u2019Elia","year":"2009","unstructured":"D\u2019Elia, R., Behnke, J. M., Bradley, J. E. & Else, K. J. Regulatory T cells. J. Immunol. 182(4), 2340\u20132348. https:\/\/doi.org\/10.4049\/jimmunol.0802767 (2009).","journal-title":"J. Immunol."},{"issue":"11","key":"35940_CR10","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1084\/jem.20101074","volume":"207","author":"JR Grainger","year":"2010","unstructured":"Grainger, J. R. et al. Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-\u03b2 pathway. J. Exp. Med. 207(11), 2331\u20132341. https:\/\/doi.org\/10.1084\/jem.20101074 (2010).","journal-title":"J. Exp. Med."},{"issue":"9","key":"35940_CR11","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/j.1365-3024.2008.01045.x","volume":"30","author":"W Harnett","year":"2008","unstructured":"Harnett, W. & Harnett, M. M. Lymphocyte hyporesponsiveness during filarial nematode infection. Parasite Immunol. 30(9), 447\u2013453. https:\/\/doi.org\/10.1111\/j.1365-3024.2008.01045.x (2008).","journal-title":"Parasite Immunol."},{"issue":"9","key":"35940_CR12","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1002\/eji.1830270920","volume":"27","author":"S Hartmann","year":"1997","unstructured":"Hartmann, S., Kyewski, B., Sonnenburg, B. & Lucius, R. A filarial cysteine protease inhibitor down-regulates T cell proliferation and enhances interleukin-10 production. Eur. J. Immunol. 27(9), 2253\u20132260. https:\/\/doi.org\/10.1002\/eji.1830270920 (1997).","journal-title":"Eur. J. Immunol."},{"issue":"3","key":"35940_CR13","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/1521-4141(200203)32:3<858::AID-IMMU858>3.0.CO;2-E","volume":"32","author":"JS Jenson","year":"2002","unstructured":"Jenson, J. S., O\u2019Connor, R., Osborne, J. & Devaney, E. Infection with Brugia microfilariae induces apoptosis of CD4+ T lymphocytes: A mechanism of immune unresponsiveness in filariasis. Eur. J. Immunol. 32(3), 858\u2013867. https:\/\/doi.org\/10.1002\/1521-4141(200203)32:3%3c858::AID-IMMU858%3e3.0.CO;2-E (2002).","journal-title":"Eur. J. Immunol."},{"issue":"4","key":"35940_CR14","doi-asserted-by":"publisher","first-page":"e12421","DOI":"10.1111\/pim.12421","volume":"39","author":"R Mishra","year":"2017","unstructured":"Mishra, R., Panda, S. K., Sahoo, P. K., Bal, M. S. & Satapathy, A. K. Increased Fas ligand expression of peripheral B-1 cells correlated with CD4+ T-cell apoptosis in filarial-infected patients. Parasite Immunol. 39(4), e12421. https:\/\/doi.org\/10.1111\/pim.12421 (2017).","journal-title":"Parasite Immunol."},{"issue":"1","key":"35940_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms6488","volume":"5","author":"AH Buck","year":"2014","unstructured":"Buck, A. H. et al. Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat. Commun. 5(1), 1. https:\/\/doi.org\/10.1038\/ncomms6488 (2014).","journal-title":"Nat. Commun."},{"issue":"8","key":"35940_CR16","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1016\/j.celrep.2017.05.001","volume":"19","author":"G Coakley","year":"2017","unstructured":"Coakley, G. et al. Extracellular vesicles from a helminth parasite suppress macrophage activation and constitute an effective vaccine for protective immunity. Cell Rep. 19(8), 1545\u20131557. https:\/\/doi.org\/10.1016\/j.celrep.2017.05.001 (2017).","journal-title":"Cell Rep."},{"issue":"4","key":"35940_CR17","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1182\/blood-2008-04-149856","volume":"112","author":"RT Semnani","year":"2008","unstructured":"Semnani, R. T. et al. Inhibition of TLR3 and TLR4 function and expression in human dendritic cells by helminth parasites. Blood 112(4), 1290\u20131298. https:\/\/doi.org\/10.1182\/blood-2008-04-149856 (2008).","journal-title":"Blood"},{"issue":"4","key":"35940_CR18","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1371\/journal.pntd.0000420","volume":"3","author":"S Babu","year":"2009","unstructured":"Babu, S. et al. Filarial lymphedema is characterized by antigen-specific Th1 and Th17 proinflammatory responses and a lack of regulatory T cells. PLOS Neglected Trop. Dis. 3(4), 420. https:\/\/doi.org\/10.1371\/journal.pntd.0000420 (2009).","journal-title":"PLOS Neglected Trop. Dis."},{"issue":"11","key":"35940_CR19","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1038\/nm1654","volume":"13","author":"AJ Melendez","year":"2007","unstructured":"Melendez, A. J. et al. Inhibition of Fc epsilon RI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes. Nat. Med. 13(11), 1375\u20131381. https:\/\/doi.org\/10.1038\/nm1654 (2007).","journal-title":"Nat. Med."},{"issue":"7","key":"35940_CR20","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/gene.2014.38","volume":"15","author":"MK Ottow","year":"2014","unstructured":"Ottow, M. K. et al. The helminth Trichuris suis suppresses TLR4-induced inflammatory responses in human macrophages. Genes Immun. 15(7), 7. https:\/\/doi.org\/10.1038\/gene.2014.38 (2014).","journal-title":"Genes Immun."},{"issue":"10","key":"35940_CR21","doi-asserted-by":"publisher","first-page":"3168","DOI":"10.1002\/art.34581","volume":"64","author":"MA Pineda","year":"2012","unstructured":"Pineda, M. A. et al. The parasitic helminth product ES-62 suppresses pathogenesis in collagen-induced arthritis by targeting the interleukin-17\u2013producing cellular network at multiple sites. Arthritis Rheum. 64(10), 3168\u20133178. https:\/\/doi.org\/10.1002\/art.34581 (2012).","journal-title":"Arthritis Rheum."},{"issue":"4","key":"35940_CR22","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1172\/JCI116752","volume":"92","author":"CL King","year":"1993","unstructured":"King, C. L. et al. Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J. Clin. Invest. 92(4), 1667\u20131673 (1993).","journal-title":"J. Clin. Invest."},{"issue":"7","key":"35940_CR23","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1046\/j.1365-3024.2001.00399.x","volume":"23","author":"TB Nutman","year":"2001","unstructured":"Nutman, T. B. & Kumaraswami, V. Regulation of the immune response in lymphatic filariasis: perspectives on acute and chronic infection with Wuchereria bancrofti in South India. Parasite Immunol. 23(7), 389\u2013399. https:\/\/doi.org\/10.1046\/j.1365-3024.2001.00399.x (2001).","journal-title":"Parasite Immunol."},{"issue":"10","key":"35940_CR24","doi-asserted-by":"publisher","first-page":"6346","DOI":"10.4049\/jimmunol.173.10.6346","volume":"173","author":"NE Mangan","year":"2004","unstructured":"Mangan, N. E. et al. Helminth infection protects mice from anaphylaxis via IL-10-producing B cells. J. Immunol. 173(10), 6346\u20136356. https:\/\/doi.org\/10.4049\/jimmunol.173.10.6346 (2004).","journal-title":"J. Immunol."},{"issue":"2","key":"35940_CR25","doi-asserted-by":"publisher","first-page":"216","DOI":"10.2307\/3281594","volume":"72","author":"BM Christensen","year":"1986","unstructured":"Christensen, B. M. & LaFond, M. M. Parasite-induced suppression of the immune response in Aedes aegypti by Brugia pahangi. J. Parasitol. 72(2), 216\u2013219. https:\/\/doi.org\/10.2307\/3281594 (1986).","journal-title":"J. Parasitol."},{"issue":"1","key":"35940_CR26","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/1471-2164-11-225","volume":"11","author":"MM Kariuki","year":"2010","unstructured":"Kariuki, M. M., Hearne, L. B. & Beerntsen, B. T. Differential transcript expression between the microfilariae of the filarial nematodes, Brugia malayi and B pahangi. BMC Genom. 11(1), 225. https:\/\/doi.org\/10.1186\/1471-2164-11-225 (2010).","journal-title":"BMC Genom."},{"issue":"3","key":"35940_CR27","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.vetpar.2006.09.037","volume":"144","author":"BT Beerntsen","year":"2007","unstructured":"Beerntsen, B. T., Bartholomay, L. C. & Lowery, R. J. Penetration of the mosquito midgut is not required for Brugia pahangi microfilariae to avoid the melanotic encapsulation response of Armigeres subalbatus. Vet. Parasitol. 144(3), 371\u2013374. https:\/\/doi.org\/10.1016\/j.vetpar.2006.09.037 (2007).","journal-title":"Vet. Parasitol."},{"issue":"4","key":"35940_CR28","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.pt.2005.02.007","volume":"21","author":"BM Christensen","year":"2005","unstructured":"Christensen, B. M., Li, J., Chen, C.-C. & Nappi, A. J. Melanization immune responses in mosquito vectors. Trends Parasitol. 21(4), 192\u2013199. https:\/\/doi.org\/10.1016\/j.pt.2005.02.007 (2005).","journal-title":"Trends Parasitol."},{"issue":"3","key":"35940_CR29","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/j.1600-0749.1993.tb00590.x","volume":"6","author":"AJ Nappi","year":"1993","unstructured":"Nappi, A. J. & Vass, E. Melanogenesis and the generation of cytotoxic molecules during insect cellular immune reactions. Pigment Cell Res. 6(3), 117\u2013126. https:\/\/doi.org\/10.1111\/j.1600-0749.1993.tb00590.x (1993).","journal-title":"Pigment Cell Res."},{"issue":"2","key":"35940_CR30","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/0014-4894(76)90125-9","volume":"39","author":"TG Andreadis","year":"1976","unstructured":"Andreadis, T. G. & Hall, D. W. Neoaplectana carpocapsae: Encapsulation in Aedes aegypti and changes in host hemocytes and hemolymph proteins. Exp. Parasitol. 39(2), 252\u2013261. https:\/\/doi.org\/10.1016\/0014-4894(76)90125-9 (1976).","journal-title":"Exp. Parasitol."},{"issue":"4","key":"35940_CR31","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/0145-305X(83)90094-0","volume":"7","author":"L Drif","year":"1983","unstructured":"Drif, L. & Breh\u00e9lin, M. The circulating hemocytes of Culexpipiens and Aedesaegypii: Cytology histochemistry, hemograms and functions. Dev. Comp. Immunol. 7(4), 687\u2013690. https:\/\/doi.org\/10.1016\/0145-305X(83)90094-0 (1983).","journal-title":"Dev. Comp. Immunol."},{"issue":"1","key":"35940_CR32","doi-asserted-by":"publisher","first-page":"76","DOI":"10.2307\/3282940","volume":"75","author":"BT Beerntsen","year":"1989","unstructured":"Beerntsen, B. T., Luckhart, S. & Christensen, B. M. Brugia malayi and Brugia pahangi: Inherent Difference in Immune Activation in the Mosquitoes Armigeres subalbatus and Aedes aegypti. J. Parasitol. 75(1), 76\u201381. https:\/\/doi.org\/10.2307\/3282940 (1989).","journal-title":"J. Parasitol."},{"issue":"3","key":"35940_CR33","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1006\/expr.1994.1094","volume":"79","author":"BT Beerntsen","year":"1994","unstructured":"Beerntsen, B. T., Severson, D. W. & Christensen, B. M. Aedes aegypti: Characterization of a hemolymph polypeptide expressed during melanotic encapsulation of filarial worms. Exp. Parasitol. 79(3), 312\u2013321. https:\/\/doi.org\/10.1006\/expr.1994.1094 (1994).","journal-title":"Exp. Parasitol."},{"issue":"5","key":"35940_CR34","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/0145-305X(94)90002-7","volume":"18","author":"S Paskewitz","year":"1994","unstructured":"Paskewitz, S. & Riehle, M. A. Response of Plasmodium refractory and susceptible strains of Anopheles gambiae to inoculated Sephadex beads. Dev. Comp. Immunol. 18(5), 369\u2013375. https:\/\/doi.org\/10.1016\/0145-305X(94)90002-7 (1994).","journal-title":"Dev. Comp. Immunol."},{"issue":"1","key":"35940_CR35","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1093\/jmedent\/34.1.56","volume":"34","author":"MS Cupp","year":"1997","unstructured":"Cupp, M. S., Chen, Y. & Cupp, E. W. Cellular Hemolymph Response of Simulium vittatum (Diptera: Simuliidae) to Intrathoracic Injection of Onchocerca lienalis (Filarioidea: Onchocercidae) Microfilariae. J. Med. Entomol. 34(1), 56\u201363. https:\/\/doi.org\/10.1093\/jmedent\/34.1.56 (1997).","journal-title":"J. Med. Entomol."},{"issue":"4","key":"35940_CR36","doi-asserted-by":"publisher","first-page":"446","DOI":"10.4269\/ajtmh.1997.56.446","volume":"56","author":"MJ Gorman","year":"1997","unstructured":"Gorman, M. J. & Paskewitz, S. M. A genetic study of a melanization response to sephadex beads in plasmodium-refractory and -susceptible strains of Anopheles gambiae. Am. J. Trop. Med. Hyg. 56(4), 446\u2013451. https:\/\/doi.org\/10.4269\/ajtmh.1997.56.446 (1997).","journal-title":"Am. J. Trop. Med. Hyg."},{"issue":"4","key":"35940_CR37","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/0020-7519(85)90028-1","volume":"15","author":"CC Chen","year":"1985","unstructured":"Chen, C. C. & Laurence, B. R. An ultrastructural study on the encapsulation of microfilariae of Brugia pahangi in the haemocoel of Anopheles quadrimaculatus. Int. J. Parasitol. 15(4), 421\u2013428. https:\/\/doi.org\/10.1016\/0020-7519(85)90028-1 (1985).","journal-title":"Int. J. Parasitol."},{"issue":"1","key":"35940_CR38","doi-asserted-by":"publisher","first-page":"133","DOI":"10.2307\/3283356","volume":"80","author":"ML Chikilian","year":"1994","unstructured":"Chikilian, M. L., Bradley, T. J., Nayar, J. K. & Knight, J. W. Ultrastructural comparison of extracellular and intracellular encapsulation of Brugia malayi in Anopheles quadrimaculatus. J. Parasitol. 80(1), 133\u2013140 (1994).","journal-title":"J. Parasitol."},{"issue":"1","key":"35940_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1570-7458.2011.01187.x","volume":"142","author":"I Gonz\u00e1lez-Santoyo","year":"2012","unstructured":"Gonz\u00e1lez-Santoyo, I. & C\u00f3rdoba-Aguilar, A. Phenoloxidase: a key component of the insect immune system. Entomol. Exp. Appl. 142(1), 1\u201316. https:\/\/doi.org\/10.1111\/j.1570-7458.2011.01187.x (2012).","journal-title":"Entomol. Exp. Appl."},{"issue":"1","key":"35940_CR40","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/j.0105-2896.2004.00116.x","volume":"198","author":"L Cerenius","year":"2004","unstructured":"Cerenius, L. & S\u00f6derh\u00e4ll, K. The prophenoloxidase-activating system in invertebrates. Immunol. Rev. 198(1), 116\u2013126. https:\/\/doi.org\/10.1111\/j.0105-2896.2004.00116.x (2004).","journal-title":"Immunol. Rev."},{"key":"35940_CR41","volume-title":"Advances in Insect Physiology (Vol. 52, pp. 83\u2013109)","author":"J Nakhleh","year":"2017","unstructured":"Nakhleh, J., El Moussawi, L. & Osta, M. A. The Melanization Response in Insect Immunity. In Advances in Insect Physiology (Vol. 52, pp. 83\u2013109) (ed. Ligoxygakis, P.) (Academic Press, 2017)."},{"issue":"3","key":"35940_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/insects9030095","volume":"9","author":"A Kumar","year":"2018","unstructured":"Kumar, A. et al. Mosquito Innate Immunity. Insects 9(3), 1. https:\/\/doi.org\/10.3390\/insects9030095 (2018).","journal-title":"Insects"},{"issue":"10","key":"35940_CR43","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/S0965-1748(02)00092-9","volume":"32","author":"MD Lavine","year":"2002","unstructured":"Lavine, M. D. & Strand, M. R. Insect hemocytes and their role in immunity. Insect. Biochem. Mol. Biol. 32(10), 1295\u20131309. https:\/\/doi.org\/10.1016\/S0965-1748(02)00092-9 (2002).","journal-title":"Insect. Biochem. Mol. Biol."},{"issue":"7","key":"35940_CR44","doi-asserted-by":"publisher","first-page":"3711","DOI":"10.1073\/pnas.1909369117","volume":"117","author":"EB Edgerton","year":"2020","unstructured":"Edgerton, E. B. et al. Activation of mosquito immunity blocks the development of transmission-stage filarial nematodes. Proc. Natl. Acad. Sci. USA 117(7), 3711\u20133717. https:\/\/doi.org\/10.1073\/pnas.1909369117 (2020).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"35940_CR45","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1186\/1471-2164-8-463","volume":"8","author":"MT Aliota","year":"2007","unstructured":"Aliota, M. T., Fuchs, J. F., Mayhew, G. F., Chen, C.-C. & Christensen, B. M. Mosquito transcriptome changes and filarial worm resistance in Armigeres subalbatus. BMC Genom. 8, 463. https:\/\/doi.org\/10.1186\/1471-2164-8-463 (2007).","journal-title":"BMC Genom."},{"issue":"6000","key":"35940_CR46","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1126\/science.1193162","volume":"330","author":"LC Bartholomay","year":"2010","unstructured":"Bartholomay, L. C. et al. Pathogenomics of Culex quinquefasciatus and meta-analysis of infection responses to diverse pathogens. Science 330(6000), 88\u201390. https:\/\/doi.org\/10.1126\/science.1193162 (2010).","journal-title":"Science"},{"issue":"10","key":"35940_CR47","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1371\/journal.pntd.0000529","volume":"3","author":"SM Erickson","year":"2009","unstructured":"Erickson, S. M. et al. Mosquito infection responses to developing filarial worms. PLOS Negl. Trop. Dis. 3(10), 529. https:\/\/doi.org\/10.1371\/journal.pntd.0000529 (2009).","journal-title":"PLOS Negl. Trop. Dis."},{"issue":"1","key":"35940_CR48","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1186\/1471-2164-8-462","volume":"8","author":"GF Mayhew","year":"2007","unstructured":"Mayhew, G. F. et al. Construction and characterization of an expressed sequenced tag library for the mosquito vector Armigeres subalbatus. BMC Genom. 8(1), 462. https:\/\/doi.org\/10.1186\/1471-2164-8-462 (2007).","journal-title":"BMC Genom."},{"issue":"3","key":"35940_CR49","doi-asserted-by":"publisher","first-page":"1004765","DOI":"10.1371\/journal.ppat.1004765","volume":"11","author":"P Juneja","year":"2015","unstructured":"Juneja, P. et al. Exome and transcriptome sequencing of Aedes aegypti identifies a locus that confers resistance to Brugia malayi and alters the immune response. PLoS Pathog. 11(3), 1004765. https:\/\/doi.org\/10.1371\/journal.ppat.1004765 (2015).","journal-title":"PLoS Pathog."},{"issue":"5","key":"35940_CR50","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.1371\/journal.pntd.0002905","volume":"8","author":"Y-J Choi","year":"2014","unstructured":"Choi, Y.-J., Aliota, M. T., Mayhew, G. F., Erickson, S. M. & Christensen, B. M. Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions. PLOS Negl. Trop. Dis. 8(5), 2905. https:\/\/doi.org\/10.1371\/journal.pntd.0002905 (2014).","journal-title":"PLOS Negl. Trop. Dis."},{"issue":"9","key":"35940_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pntd.0004069","volume":"9","author":"M Zamanian","year":"2015","unstructured":"Zamanian, M. et al. Release of small RNA-containing exosome-like vesicles from the human filarial parasite Brugia malayi. PLoS Negl Trop Dis 9(9), 1. https:\/\/doi.org\/10.1371\/journal.pntd.0004069 (2015).","journal-title":"PLoS Negl Trop Dis"},{"key":"35940_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vetpar.2016.11.005","volume":"232","author":"L Tritten","year":"2016","unstructured":"Tritten, L., Clarke, D., Timmins, S., McTier, T. & Geary, T. G. Dirofilaria immitis exhibits sex- and stage-specific differences in excretory\/secretory miRNA and protein profiles. Vet. Parasitol. 232, 1\u20137. https:\/\/doi.org\/10.1016\/j.vetpar.2016.11.005 (2016).","journal-title":"Vet. Parasitol."},{"issue":"4","key":"35940_CR53","doi-asserted-by":"publisher","first-page":"e0006438","DOI":"10.1371\/journal.pntd.0006438","volume":"12","author":"H Harischandra","year":"2018","unstructured":"Harischandra, H., Yuan, W., Loghry, H. J., Zamanian, M. & Kimber, M. J. Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin. PLOS Neglec. Trop. Dis. 12(4), e0006438. https:\/\/doi.org\/10.1371\/journal.pntd.0006438 (2018).","journal-title":"PLOS Neglec. Trop. Dis."},{"issue":"2","key":"35940_CR54","doi-asserted-by":"publisher","first-page":"e12036","DOI":"10.1002\/jev2.12036","volume":"10","author":"HJ Loghry","year":"2020","unstructured":"Loghry, H. J. et al. Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes. J. Extracell. Vesic. 10(2), e12036. https:\/\/doi.org\/10.1002\/jev2.12036 (2020).","journal-title":"J. Extracell. Vesic."},{"issue":"8","key":"35940_CR55","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/nri855","volume":"2","author":"C Thery","year":"2002","unstructured":"Thery, C., Zitvogel, L. & Amigorena, S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2(8), 569 (2002).","journal-title":"Nat. Rev. Immunol."},{"issue":"6","key":"35940_CR56","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/ncb1596","volume":"9","author":"H Valadi","year":"2007","unstructured":"Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9(6), 654 (2007).","journal-title":"Nat. Cell Biol."},{"issue":"12","key":"35940_CR57","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1111\/j.1600-0854.2011.01225.x","volume":"12","author":"A Bobrie","year":"2011","unstructured":"Bobrie, A., Colombo, M., Raposo, G. & Th\u00e9ry, C. Exosome secretion: Molecular mechanisms and roles in immune responses. Traffic 12(12), 1659\u20131668. https:\/\/doi.org\/10.1111\/j.1600-0854.2011.01225.x (2011).","journal-title":"Traffic"},{"issue":"3","key":"35940_CR58","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1084\/jem.183.3.1161","volume":"183","author":"G Raposo","year":"1996","unstructured":"Raposo, G. et al. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183(3), 1161\u20131172. https:\/\/doi.org\/10.1084\/jem.183.3.1161 (1996).","journal-title":"J. Exp. Med."},{"issue":"7","key":"35940_CR59","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/j.bbagen.2012.03.017","volume":"1820","author":"AV Vlassov","year":"2012","unstructured":"Vlassov, A. V., Magdaleno, S., Setterquist, R. & Conrad, R. Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochimica et Biophysica Acta (BBA) General Subjects 1820(7), 940\u2013948. https:\/\/doi.org\/10.1016\/j.bbagen.2012.03.017 (2012).","journal-title":"Biochimica et Biophysica Acta (BBA) General Subjects"},{"issue":"1","key":"35940_CR60","doi-asserted-by":"publisher","first-page":"e0008884","DOI":"10.1371\/journal.pntd.0008884","volume":"15","author":"A Ricciardi","year":"2021","unstructured":"Ricciardi, A. et al. Extracellular vesicles released from the filarial parasite Brugia malayi downregulate the host mTOR pathway. PLOS Negl. Trop. Dis. 15(1), e0008884. https:\/\/doi.org\/10.1371\/journal.pntd.0008884 (2021).","journal-title":"PLOS Negl. Trop. Dis."},{"issue":"11","key":"35940_CR61","doi-asserted-by":"publisher","first-page":"e0006056","DOI":"10.1371\/journal.pntd.0006056","volume":"11","author":"HY Gu","year":"2017","unstructured":"Gu, H. Y. et al. Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of Haemonchus contortus. PLOS Negl. Trop. Dis. 11(11), e0006056. https:\/\/doi.org\/10.1371\/journal.pntd.0006056 (2017).","journal-title":"PLOS Negl. Trop. Dis."},{"key":"35940_CR62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2018.00850","volume":"9","author":"RM Eichenberger","year":"2018","unstructured":"Eichenberger, R. M. et al. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front. Immunol. 9, 1. https:\/\/doi.org\/10.3389\/fimmu.2018.00850 (2018).","journal-title":"Front. Immunol."},{"issue":"1","key":"35940_CR63","doi-asserted-by":"publisher","first-page":"1428004","DOI":"10.1080\/20013078.2018.1428004","volume":"7","author":"RM Eichenberger","year":"2018","unstructured":"Eichenberger, R. M. et al. Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host\u2013parasite communication. J. Extracell. Vesic. 7(1), 1428004. https:\/\/doi.org\/10.1080\/20013078.2018.1428004 (2018).","journal-title":"J. Extracell. Vesic."},{"key":"35940_CR64","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.vetpar.2016.03.008","volume":"221","author":"T Tzelos","year":"2016","unstructured":"Tzelos, T. et al. A preliminary proteomic characterisation of extracellular vesicles released by the ovine parasitic nematode, Teladorsagia circumcincta. Vet. Parasitol. 221, 84\u201392. https:\/\/doi.org\/10.1016\/j.vetpar.2016.03.008 (2016).","journal-title":"Vet. Parasitol."},{"issue":"1","key":"35940_CR65","doi-asserted-by":"publisher","first-page":"1578116","DOI":"10.1080\/20013078.2019.1578116","volume":"8","author":"EP Hansen","year":"2019","unstructured":"Hansen, E. P. et al. Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite\u2013host cross talk. J. Extracell. Vesic. 8(1), 1578116. https:\/\/doi.org\/10.1080\/20013078.2019.1578116 (2019).","journal-title":"J. Extracell. Vesic."},{"key":"35940_CR66","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.exppara.2017.05.003","volume":"178","author":"L Tritten","year":"2017","unstructured":"Tritten, L. et al. Excretory\/secretory products from the gastrointestinal nematode Trichuris muris. Exp. Parasitol. 178, 30\u201336. https:\/\/doi.org\/10.1016\/j.exppara.2017.05.003 (2017).","journal-title":"Exp. Parasitol."},{"issue":"7","key":"35940_CR67","doi-asserted-by":"publisher","first-page":"e12536","DOI":"10.1111\/pim.12536","volume":"40","author":"RK Shears","year":"2018","unstructured":"Shears, R. K., Bancroft, A. J., Hughes, G. W., Grencis, R. K. & Thornton, D. J. Extracellular vesicles induce protective immunity against Trichuris muris. Parasite Immunol. 40(7), e12536. https:\/\/doi.org\/10.1111\/pim.12536 (2018).","journal-title":"Parasite Immunol."},{"issue":"3","key":"35940_CR68","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1645\/14-714.1","volume":"101","author":"EP Hansen","year":"2015","unstructured":"Hansen, E. P., Kringel, H., Williams, A. R. & Nejsum, P. Secretion of RNA-containing extracellular vesicles by the porcine Whipworm, Trichuris Suis. J. Parasitol. 101(3), 336\u2013340 (2015).","journal-title":"J. Parasitol."},{"issue":"10","key":"35940_CR69","doi-asserted-by":"publisher","first-page":"e12665","DOI":"10.1111\/pim.12665","volume":"41","author":"M Kosanovi\u0107","year":"2019","unstructured":"Kosanovi\u0107, M. et al. Trichinella spiralis muscle larvae release extracellular vesicles with immunomodulatory properties. Parasite Immunol. 41(10), e12665. https:\/\/doi.org\/10.1111\/pim.12665 (2019).","journal-title":"Parasite Immunol."},{"issue":"9","key":"35940_CR70","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.ijpara.2020.06.001","volume":"50","author":"MA Duque-Correa","year":"2020","unstructured":"Duque-Correa, M. A. et al. Development of caecaloids to study host\u2013pathogen interactions: New insights into immunoregulatory functions of Trichuris muris extracellular vesicles in the caecum. Int. J. Parasitol. 50(9), 707\u2013718. https:\/\/doi.org\/10.1016\/j.ijpara.2020.06.001 (2020).","journal-title":"Int. J. Parasitol."},{"issue":"1","key":"35940_CR71","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/1756-3305-5-148","volume":"5","author":"ABF Barletta","year":"2012","unstructured":"Barletta, A. B. F., Silva, M. C. L. N. & Sorgine, M. H. F. Validation of Aedes aegypti Aag-2 cells as a model for insect immune studies. Parasit. Vectors 5(1), 148. https:\/\/doi.org\/10.1186\/1756-3305-5-148 (2012).","journal-title":"Parasit. Vectors"},{"issue":"3","key":"35940_CR72","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/S0965-1748(00)00146-6","volume":"31","author":"AM Fallon","year":"2001","unstructured":"Fallon, A. M. & Sun, D. Exploration of mosquito immunity using cells in culture. Insect. Biochem. Mol. Biol. 31(3), 263\u2013278. https:\/\/doi.org\/10.1016\/S0965-1748(00)00146-6 (2001).","journal-title":"Insect. Biochem. Mol. Biol."},{"issue":"5","key":"35940_CR73","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1083\/jcb.123.5.1107","volume":"123","author":"LH Wang","year":"1993","unstructured":"Wang, L. H., Rothberg, K. G. & Anderson, R. G. Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation. J. Cell Biol. 123(5), 1107\u20131117. https:\/\/doi.org\/10.1083\/jcb.123.5.1107 (1993).","journal-title":"J. Cell Biol."},{"issue":"3","key":"35940_CR74","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/mt.2009.281","volume":"18","author":"D Vercauteren","year":"2010","unstructured":"Vercauteren, D. et al. The use of inhibitors to study endocytic pathways of gene carriers: Optimization and Pitfalls. Mol. Ther. 18(3), 561\u2013569. https:\/\/doi.org\/10.1038\/mt.2009.281 (2010).","journal-title":"Mol. Ther."},{"issue":"4","key":"35940_CR75","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1111\/j.1600-0854.2007.00540.x","volume":"8","author":"CK Payne","year":"2007","unstructured":"Payne, C. K., Jones, S. A., Chen, C. & Zhuang, X. Internalization and trafficking of cell surface proteoglycans and proteoglycan-binding ligands. Traffic 8(4), 389\u2013401. https:\/\/doi.org\/10.1111\/j.1600-0854.2007.00540.x (2007).","journal-title":"Traffic"},{"issue":"4","key":"35940_CR76","doi-asserted-by":"publisher","first-page":"4444","DOI":"10.1021\/acsnano.9b10033","volume":"14","author":"BS Joshi","year":"2020","unstructured":"Joshi, B. S., de Beer, M. A., Giepmans, B. N. G. & Zuhorn, I. S. Endocytosis of extracellular vesicles and release of their Cargo from endosomes. ACS Nano 14(4), 4444\u20134455. https:\/\/doi.org\/10.1021\/acsnano.9b10033 (2020).","journal-title":"ACS Nano"},{"issue":"20","key":"35940_CR77","doi-asserted-by":"publisher","first-page":"6953","DOI":"10.1093\/nar\/gkm686","volume":"35","author":"F Winter","year":"2007","unstructured":"Winter, F., Edaye, S., H\u00fcttenhofer, A. & Brunel, C. Anopheles gambiae miRNAs as actors of defence reaction against Plasmodium invasion. Nucl. Acids Res. 35(20), 6953\u20136962. https:\/\/doi.org\/10.1093\/nar\/gkm686 (2007).","journal-title":"Nucl. Acids Res."},{"issue":"1","key":"35940_CR78","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1111\/imb.12070","volume":"23","author":"CL Campbell","year":"2014","unstructured":"Campbell, C. L., Harrison, T., Hess, A. M. & Ebel, G. D. MicroRNA levels are modulated in Aedes aegypti after exposure to Dengue-2. Insect Mol. Biol. 23(1), 132\u2013139. https:\/\/doi.org\/10.1111\/imb.12070 (2014).","journal-title":"Insect Mol. Biol."},{"issue":"22","key":"35940_CR79","doi-asserted-by":"publisher","first-page":"9250","DOI":"10.1073\/pnas.1105469108","volume":"108","author":"M Hussain","year":"2011","unstructured":"Hussain, M., Frentiu, F. D., Moreira, L. A., O\u2019Neill, S. L. & Asgari, S. Wolbachia uses host microRNAs to manipulate host gene expression and facilitate colonization of the dengue vector Aedes aegypti. PNAS 108(22), 9250\u20139255. https:\/\/doi.org\/10.1073\/pnas.1105469108 (2011).","journal-title":"PNAS"},{"issue":"D1","key":"35940_CR80","doi-asserted-by":"publisher","first-page":"D898","DOI":"10.1093\/nar\/gkab929","volume":"50","author":"B Amos","year":"2022","unstructured":"Amos, B. et al. VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center. Nucl. Acids Res. 50(D1), D898\u2013D911. https:\/\/doi.org\/10.1093\/nar\/gkab929 (2022).","journal-title":"Nucl. Acids Res."},{"issue":"1","key":"35940_CR81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13071-018-3120-1","volume":"11","author":"W Dedkhad","year":"2018","unstructured":"Dedkhad, W. et al. Immune responses of Aedes togoi, Anopheles paraliae and Anopheles lesteri against nocturnally subperiodic Brugia malayi microfilariae during migration from the midgut to the site of development. Parasites Vectors 11(1), 1. https:\/\/doi.org\/10.1186\/s13071-018-3120-1 (2018).","journal-title":"Parasites Vectors"},{"issue":"3\u20134","key":"35940_CR82","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1093\/jmedent\/3.3-4.239","volume":"3","author":"CP Ramachandran","year":"1966","unstructured":"Ramachandran, C. P. Biological aspects in the transmission of Brugia Malayi by Aedes Aegypti in the laboratory1. J. Med. Entomol. 3(3\u20134), 239\u2013252. https:\/\/doi.org\/10.1093\/jmedent\/3.3-4.239 (1966).","journal-title":"J. Med. Entomol."},{"key":"35940_CR83","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1590\/S0074-02761999000500005","volume":"94","author":"CM Albuquerque","year":"1999","unstructured":"Albuquerque, C. M. et al. Bloodmeal microfilariae density and the uptake and establishment of Wuchereria bancrofti infections in Culex quinquefasciatus and Aedes aegypti. Mem. Inst. Oswaldo Cruz 94, 591\u2013596. https:\/\/doi.org\/10.1590\/S0074-02761999000500005 (1999).","journal-title":"Mem. Inst. Oswaldo Cruz"},{"issue":"1","key":"35940_CR84","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/s13071-017-2302-6","volume":"10","author":"GP League","year":"2017","unstructured":"League, G. P., Est\u00e9vez-Lao, T. Y., Yan, Y., Garcia-Lopez, V. A. & Hillyer, J. F. Anopheles gambiae larvae mount stronger immune responses against bacterial infection than adults: Evidence of adaptive decoupling in mosquitoes. Parasit. Vectors 10(1), 367. https:\/\/doi.org\/10.1186\/s13071-017-2302-6 (2017).","journal-title":"Parasit. Vectors"},{"key":"35940_CR85","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.dci.2015.12.006","volume":"58","author":"JF Hillyer","year":"2016","unstructured":"Hillyer, J. F. Insect immunology and hematopoiesis. Dev. Comp. Immunol. 58, 102\u2013118. https:\/\/doi.org\/10.1016\/j.dci.2015.12.006 (2016).","journal-title":"Dev. Comp. Immunol."},{"issue":"8","key":"35940_CR86","doi-asserted-by":"publisher","first-page":"e102568","DOI":"10.1371\/journal.pone.0102568","volume":"9","author":"MR Schmid","year":"2014","unstructured":"Schmid, M. R. et al. Control of drosophila blood cell activation via toll signaling in the fat body. PLoS ONE 9(8), e102568. https:\/\/doi.org\/10.1371\/journal.pone.0102568 (2014).","journal-title":"PLoS ONE"},{"issue":"3","key":"35940_CR87","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1111\/j.1365-3024.2009.01172.x","volume":"32","author":"N Balasubramanian","year":"2010","unstructured":"Balasubramanian, N., Toubarro, D. & Sim\u00f5es, N. Biochemical study and in vitro insect immune suppression by a trypsin-like secreted protease from the nematode Steinernema carpocapsae. Parasite Immunol. 32(3), 165\u2013175. https:\/\/doi.org\/10.1111\/j.1365-3024.2009.01172.x (2010).","journal-title":"Parasite Immunol."},{"issue":"9","key":"35940_CR88","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.ijpara.2009.01.012","volume":"39","author":"N Balasubramanian","year":"2009","unstructured":"Balasubramanian, N., Hao, Y.-J., Toubarro, D., Nascimento, G. & Sim\u00f5es, N. Purification, biochemical and molecular analysis of a chymotrypsin protease with prophenoloxidase suppression activity from the entomopathogenic nematode Steinernema carpocapsae. Int. J. Parasitol. 39(9), 975\u2013984. https:\/\/doi.org\/10.1016\/j.ijpara.2009.01.012 (2009).","journal-title":"Int. J. Parasitol."},{"issue":"12","key":"35940_CR89","doi-asserted-by":"publisher","first-page":"e1001239","DOI":"10.1371\/journal.ppat.1001239","volume":"6","author":"C Song","year":"2010","unstructured":"Song, C., Gallup, J. M., Day, T. A., Bartholomay, L. C. & Kimber, M. J. Development of an In Vivo RNAi Protocol to Investigate Gene Function in the Filarial Nematode, Brugia malayi. PLoS Pathog. 6(12), e1001239. https:\/\/doi.org\/10.1371\/journal.ppat.1001239 (2010).","journal-title":"PLoS Pathog."},{"key":"35940_CR90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fcell.2021.627976","volume":"9","author":"J Ramesh Kumar","year":"2022","unstructured":"Ramesh Kumar, J., Smith, J. P., Kwon, H. & Smith, R. C. Use of clodronate liposomes to deplete phagocytic immune cells in Drosophila melanogaster and Aedes aegypti. Front. Cell Dev. Biol. 9, 1. https:\/\/doi.org\/10.3389\/fcell.2021.627976 (2022).","journal-title":"Front. Cell Dev. Biol."},{"issue":"D1","key":"35940_CR91","doi-asserted-by":"publisher","first-page":"D68","DOI":"10.1093\/nar\/gkt1181","volume":"42","author":"A Kozomara","year":"2014","unstructured":"Kozomara, A. & Griffiths-Jones, S. miRBase: Annotating high confidence microRNAs using deep sequencing data. Nucl. Acids Res. 42(D1), D68\u2013D73. https:\/\/doi.org\/10.1093\/nar\/gkt1181 (2014).","journal-title":"Nucl. Acids Res."},{"issue":"1","key":"35940_CR92","doi-asserted-by":"publisher","first-page":"D152","DOI":"10.1093\/nar\/gkq1027","volume":"39","author":"A Kozomara","year":"2011","unstructured":"Kozomara, A. & Griffiths-Jones, S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucl. Acids Res. 39(1), D152\u2013D157. https:\/\/doi.org\/10.1093\/nar\/gkq1027 (2011).","journal-title":"Nucl. Acids Res."},{"issue":"D1","key":"35940_CR93","doi-asserted-by":"publisher","first-page":"D155","DOI":"10.1093\/nar\/gky1141","volume":"47","author":"A Kozomara","year":"2019","unstructured":"Kozomara, A., Birgaoanu, M. & Griffiths-Jones, S. miRBase: from microRNA sequences to function. Nucl. Acids Res. 47(D1), D155\u2013D162. https:\/\/doi.org\/10.1093\/nar\/gky1141 (2019).","journal-title":"Nucl. Acids Res."},{"issue":"1","key":"35940_CR94","doi-asserted-by":"publisher","first-page":"D154","DOI":"10.1093\/nar\/gkm952","volume":"36","author":"S Griffiths-Jones","year":"2008","unstructured":"Griffiths-Jones, S., Saini, H. K., van Dongen, S. & Enright, A. J. miRBase: Tools for microRNA genomics. Nucl. Acids Res. 36(1), D154\u2013D158. https:\/\/doi.org\/10.1093\/nar\/gkm952 (2008).","journal-title":"Nucl. Acids Res."},{"issue":"1","key":"35940_CR95","doi-asserted-by":"publisher","first-page":"D140","DOI":"10.1093\/nar\/gkj112","volume":"34","author":"S Griffiths-Jones","year":"2006","unstructured":"Griffiths-Jones, S., Grocock, R. J., van Dongen, S., Bateman, A. & Enright, A. J. miRBase: microRNA sequences, targets and gene nomenclature. Nucl. Acids Res. 34(1), D140\u2013D144. https:\/\/doi.org\/10.1093\/nar\/gkj112 (2006).","journal-title":"Nucl. Acids Res."},{"issue":"1","key":"35940_CR96","doi-asserted-by":"publisher","first-page":"D109","DOI":"10.1093\/nar\/gkh023","volume":"32","author":"S Griffiths-Jones","year":"2004","unstructured":"Griffiths-Jones, S. The microRNA Registry. Nucl. Acids Res. 32(1), D109\u2013D111. https:\/\/doi.org\/10.1093\/nar\/gkh023 (2004).","journal-title":"Nucl. Acids Res."},{"issue":"1","key":"35940_CR97","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/1471-2105-10-421","volume":"10","author":"C Camacho","year":"2009","unstructured":"Camacho, C. et al. BLAST+: Architecture and applications. BMC Bioinformatics 10(1), 421. https:\/\/doi.org\/10.1186\/1471-2105-10-421 (2009).","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"35940_CR98","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1748-7188-6-26","volume":"6","author":"R Lorenz","year":"2011","unstructured":"Lorenz, R. et al. ViennaRNA Package 2.0. Algorithms Mol. Biol. 6(1), 26. https:\/\/doi.org\/10.1186\/1748-7188-6-26 (2011).","journal-title":"Algorithms Mol. Biol."},{"issue":"7328","key":"35940_CR99","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nature09616","volume":"469","author":"RCF Calvin","year":"2011","unstructured":"Calvin, R. C. F. & Jan, H. Formation, regulation and evolution of caenorhabditis elegans 3\u2032UTRs. Nature 469(7328), 97. https:\/\/doi.org\/10.1038\/nature09616 (2011).","journal-title":"Nature"},{"issue":"6","key":"35940_CR100","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.molcel.2014.02.013","volume":"53","author":"J-W Nam","year":"2014","unstructured":"Nam, J.-W. et al. Global analyses of the effect of different cellular contexts on microRNA targeting. Mol. Cell 53(6), 1031\u20131043. https:\/\/doi.org\/10.1016\/j.molcel.2014.02.013 (2014).","journal-title":"Mol. Cell"},{"issue":"1","key":"35940_CR101","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","volume":"120","author":"BP Lewis","year":"2005","unstructured":"Lewis, B. P., Burge, C. B. & Bartel, D. P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are MicroRNA targets. Cell 120(1), 15\u201320. https:\/\/doi.org\/10.1016\/j.cell.2004.12.035 (2005).","journal-title":"Cell"},{"issue":"1","key":"35940_CR102","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1186\/gb-2003-5-1-r1","volume":"5","author":"AJ Enright","year":"2003","unstructured":"Enright, A. J. et al. MicroRNA targets in Drosophila. Genome Biol. 5(1), R1. https:\/\/doi.org\/10.1186\/gb-2003-5-1-r1 (2003).","journal-title":"Genome Biol."},{"issue":"1","key":"35940_CR103","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucl. Acids Res. 28(1), 27\u201330. https:\/\/doi.org\/10.1093\/nar\/28.1.27 (2000).","journal-title":"Nucl. Acids Res."},{"issue":"11","key":"35940_CR104","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Prot. Sci. 28(11), 1947\u20131951. https:\/\/doi.org\/10.1002\/pro.3715 (2019).","journal-title":"Prot. Sci."},{"issue":"D1","key":"35940_CR105","doi-asserted-by":"publisher","first-page":"D587","DOI":"10.1093\/nar\/gkac963","volume":"51","author":"M Kanehisa","year":"2023","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucl. Acids Res. 51(D1), D587\u2013D592. https:\/\/doi.org\/10.1093\/nar\/gkac963 (2023).","journal-title":"Nucl. Acids Res."},{"key":"35940_CR106","unstructured":"Kanehisa, \u201cKEGG Database.\u201d [Online]. Available: https:\/\/www.kegg.jp\/kegg\/kegg1.html"},{"issue":"15","key":"35940_CR107","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 30(15), 2114\u20132120. https:\/\/doi.org\/10.1093\/bioinformatics\/btu170 (2014).","journal-title":"Bioinformatics"},{"issue":"8","key":"35940_CR108","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","volume":"37","author":"D Kim","year":"2019","unstructured":"Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37(8), 907\u2013915. https:\/\/doi.org\/10.1038\/s41587-019-0201-4 (2019).","journal-title":"Nat. Biotechnol."},{"issue":"3","key":"35940_CR109","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nbt.3122","volume":"33","author":"M Pertea","year":"2015","unstructured":"Pertea, M. et al. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat. Biotechnol. 33(3), 290\u2013295. https:\/\/doi.org\/10.1038\/nbt.3122 (2015).","journal-title":"Nat. Biotechnol."},{"key":"35940_CR110","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.molbiopara.2016.11.005","volume":"215","author":"KL Howe","year":"2017","unstructured":"Howe, K. L., Bolt, B. J., Shafie, M., Kersey, P. & Berriman, M. WormBase ParaSite\u2014a comprehensive resource for helminth genomics. Mol. Biochem. Parasitol. 215, 2\u201310. https:\/\/doi.org\/10.1016\/j.molbiopara.2016.11.005 (2017).","journal-title":"Mol. Biochem. Parasitol."},{"issue":"D1","key":"35940_CR111","doi-asserted-by":"publisher","first-page":"D774","DOI":"10.1093\/nar\/gkv1217","volume":"44","author":"KL Howe","year":"2016","unstructured":"Howe, K. L. et al. WormBase 2016: expanding to enable helminth genomic research. Nucl. Acids Res. 44(D1), D774\u2013D780. https:\/\/doi.org\/10.1093\/nar\/gkv1217 (2016).","journal-title":"Nucl. Acids Res."},{"key":"35940_CR112","doi-asserted-by":"publisher","first-page":"D707","DOI":"10.1093\/nar\/gku1117","volume":"43","author":"GI Giraldo-Calder\u00f3n","year":"2015","unstructured":"Giraldo-Calder\u00f3n, G. I. et al. VectorBase: an updated bioinformatics resource for invertebrate vectors and other organisms related with human diseases. Nucl. Acids Res. 43, D707\u2013D713. https:\/\/doi.org\/10.1093\/nar\/gku1117 (2015).","journal-title":"Nucl. Acids Res."},{"key":"35940_CR113","unstructured":"Andrews, S. FastQC: A quality control tool for high throughput sequence data."},{"issue":"19","key":"35940_CR114","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","volume":"32","author":"P Ewels","year":"2016","unstructured":"Ewels, P., Magnusson, M., Lundin, S. & K\u00e4ller, M. MultiQC: Summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32(19), 3047\u20133048. https:\/\/doi.org\/10.1093\/bioinformatics\/btw354 (2016).","journal-title":"Bioinformatics"},{"key":"35940_CR115","unstructured":"Krueger, F. Trim Galore: A wrapper tool around Cutadapt and FastQC to consistently apply quality and adapter trimming to FastQ files, with some extra functionality for MspI-digested RRBS-type (Reduced Representation Bisufite-Seq) libraries."},{"issue":"4","key":"35940_CR116","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/nmeth.3317","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim, D., Langmead, B. & Salzberg, S. L. HISAT: A fast spliced aligner with low memory requirements. Nat. Methods 12(4), 4. https:\/\/doi.org\/10.1038\/nmeth.3317 (2015).","journal-title":"Nat. Methods"},{"issue":"9","key":"35940_CR117","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nprot.2016.095","volume":"11","author":"M Pertea","year":"2016","unstructured":"Pertea, M., Kim, D., Pertea, G. M., Leek, J. T. & Salzberg, S. L. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat. Protoc. 11(9), 9. https:\/\/doi.org\/10.1038\/nprot.2016.095 (2016).","journal-title":"Nat. Protoc."},{"key":"35940_CR118","doi-asserted-by":"publisher","first-page":"7732","DOI":"10.1038\/s41586-018-0692-z","volume":"563","author":"BJ Matthews","year":"2018","unstructured":"Matthews, B. J. et al. Improved reference genome of Aedes aegypti informs arbovirus vector control. Nature 563, 7732. https:\/\/doi.org\/10.1038\/s41586-018-0692-z (2018).","journal-title":"Nature"},{"key":"35940_CR119","doi-asserted-by":"publisher","unstructured":"Bruggner, R. V. A System for Integration And Management of Community Annotation for VectorBase.org. (University Of Notre Dame, 2007). https:\/\/doi.org\/10.7274\/j098z89314r.","DOI":"10.7274\/j098z89314r"},{"issue":"5845","key":"35940_CR120","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1126\/science.1145406","volume":"317","author":"E Ghedin","year":"2007","unstructured":"Ghedin, E. et al. Draft genome of the filarial nematode parasite Brugia malayi. Science 317(5845), 1756\u20131760. https:\/\/doi.org\/10.1126\/science.1145406 (2007).","journal-title":"Science"},{"key":"35940_CR121","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1007\/978-1-4939-7737-6_15","volume-title":"Eukaryotic Genomic Databases Methods and Protocols","author":"BJ Bolt","year":"2018","unstructured":"Bolt, B. J. et al. Using WormBase ParaSite: An integrated platform for exploring helminth genomic data. In Eukaryotic Genomic Databases Methods and Protocols (ed. Kollmar, M.) 471\u2013491 (Springer, New York, 2018)."},{"issue":"16","key":"35940_CR122","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. et al. The sequence alignment\/Map format and SAMtools. Bioinformatics 25(16), 2078\u20132079. https:\/\/doi.org\/10.1093\/bioinformatics\/btp352 (2009).","journal-title":"Bioinformatics"},{"issue":"10","key":"35940_CR123","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1093\/nar\/gkt214","volume":"41","author":"Y Liao","year":"2013","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. The Subread aligner: Fast, accurate and scalable read mapping by seed-and-vote. Nucl. Acids Res. 41(10), e108. https:\/\/doi.org\/10.1093\/nar\/gkt214 (2013).","journal-title":"Nucl. Acids Res."},{"issue":"12","key":"35940_CR124","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15(12), 550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8 (2014).","journal-title":"Genome Biol."},{"issue":"D1","key":"35940_CR125","doi-asserted-by":"publisher","first-page":"D506","DOI":"10.1093\/nar\/gky1049","volume":"47","author":"The UniProt Consortium","year":"2019","unstructured":"The UniProt Consortium. UniProt: A worldwide hub of protein knowledge. Nucl. Acids Res. 47(D1), D506\u2013D515. https:\/\/doi.org\/10.1093\/nar\/gky1049 (2019).","journal-title":"Nucl. Acids Res."},{"issue":"5","key":"35940_CR126","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L.-G., Han, Y. & He, Q.-Y. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 16(5), 284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118 (2012).","journal-title":"OMICS"},{"issue":"4","key":"35940_CR127","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.gpb.2021.08.001","volume":"19","author":"T Chen","year":"2021","unstructured":"Chen, T. et al. The genome sequence archive family: Toward explosive data growth and diverse data types. Genom. Proteom. Bioinf. 19(4), 578\u2013583. https:\/\/doi.org\/10.1016\/j.gpb.2021.08.001 (2021).","journal-title":"Genom. Proteom. Bioinf."},{"issue":"D1","key":"35940_CR128","doi-asserted-by":"publisher","first-page":"D27","DOI":"10.1093\/nar\/gkab951","volume":"50","author":"CNCB-NGDC Members and Partners","year":"2022","unstructured":"CNCB-NGDC Members and Partners. Database Resources of the National Genomics Data Center, China National Center for Bioinformation in 2022. Nucl. Acids Res. 50(D1), D27\u2013D38. https:\/\/doi.org\/10.1093\/nar\/gkab951 (2022).","journal-title":"Nucl. Acids Res."},{"key":"35940_CR129","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.3389\/fimmu.2021.680020","volume":"12","author":"H Kwon","year":"2021","unstructured":"Kwon, H., Hall, D. R. & Smith, R. C. Prostaglandin E2 signaling mediates oenocytoid immune cell function and lysis, limiting bacteria and plasmodium oocyst survival in Anopheles gambiae. Front. Immunol. 12, 3303. https:\/\/doi.org\/10.3389\/fimmu.2021.680020 (2021).","journal-title":"Front. Immunol."},{"issue":"28","key":"35940_CR130","doi-asserted-by":"publisher","first-page":"14119","DOI":"10.1073\/pnas.1900147116","volume":"116","author":"H Kwon","year":"2019","unstructured":"Kwon, H. & Smith, R. C. Chemical depletion of phagocytic immune cells in Anopheles gambiae reveals dual roles of mosquito hemocytes in anti-Plasmodium immunity. Proc. Natl. Acad. Sci. 116(28), 14119\u201314128. https:\/\/doi.org\/10.1073\/pnas.1900147116 (2019).","journal-title":"Proc. Natl. Acad. Sci."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-35940-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-35940-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-35940-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T10:15:46Z","timestamp":1685528146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-35940-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":130,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["35940"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-35940-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]},"assertion":[{"value":"4 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8778"}}