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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,2,18]]},"abstract":"<jats:p>\n                    Mosquito-borne helminth infections are responsible for a significant worldwide disease burden in both humans and animals. Accordingly, development of novel strategies to reduce disease transmission by targeting these pathogens in the vector are of paramount importance. We found that a strain of\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    that is refractory to infection by\n                    <jats:italic>Dirofilaria immitis<\/jats:italic>\n                    , the agent of canine heartworm disease, mounts a stronger immune response during infection than does a susceptible strain. Moreover, activation of the Toll immune signaling pathway in the susceptible strain arrests larval development of the parasite, thereby decreasing the number of transmission-stage larvae. Notably, this strategy also blocks transmission-stage\n                    <jats:italic>Brugia malayi<\/jats:italic>\n                    , an agent of human lymphatic filariasis. Our data show that mosquito immunity can play a pivotal role in restricting filarial nematode development and suggest that genetically engineering mosquitoes with enhanced immunity will help reduce pathogen transmission.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1909369117","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T20:25:42Z","timestamp":1580761542000},"page":"3711-3717","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["Activation of mosquito immunity blocks the development of transmission-stage filarial nematodes"],"prefix":"10.1073","volume":"117","author":[{"given":"Elizabeth B.","family":"Edgerton","sequence":"first","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail R.","family":"McCrea","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corbett T.","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny Y.","family":"Kwok","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letitia K.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Watson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences &amp; Advanced Medicine, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Fuller","sequence":"additional","affiliation":[{"name":"Shelter Medicine, Charleston Animal Society, North Charleston, SC 29406"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Nolan","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Lok","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3766-2097","authenticated-orcid":false,"given":"Michael","family":"Povelones","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.cvsm.2009.06.003","article-title":"Heartworm biology, treatment, and control","volume":"39","author":"Bowman D. 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Helminthol. 48, 221\u2013228 (1974).","journal-title":"J. Helminthol."},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/0022-1910(90)90044-G","article-title":"Selection of a strain of Aedes aegypti susceptible to Dirofilaria immitis and lacking intracellular concretions in the Malpighian tubules","volume":"36","author":"Bradley T. J.","year":"1990","unstructured":"T. J. Bradley, J. K. Nayar, J. W. Knight, Selection of a strain of Aedes aegypti susceptible to Dirofilaria immitis and lacking intracellular concretions in the Malpighian tubules. J. Insect Physiol. 36, 709\u2013717 (1990).","journal-title":"J. Insect Physiol."},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1080\/00034983.1962.11686134","article-title":"The selection of a strain of Aedes aegypti susceptible to infection with semi-periodic Brugia malayi","volume":"56","author":"Macdonald W. W.","year":"1962","unstructured":"W. W. 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Christensen, Induced polypeptides associated with filarial worm refractoriness in Aedes aegypti. Proc. Natl. Acad. Sci. U.S.A. 89, 6502\u20136505 (1992).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.molimm.2019.03.008","article-title":"The prophenoloxidase system in Drosophila participates in the anti-nematode immune response","volume":"109","author":"Cooper D.","year":"2019","unstructured":"D. Cooper, C. Wuebbolt, C. Heryanto, I. Eleftherianos, The prophenoloxidase system in Drosophila participates in the anti-nematode immune response. Mol. Immunol. 109, 88\u201398 (2019).","journal-title":"Mol. Immunol."},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ijpara.2006.08.009","article-title":"Relationship between the successful infection by entomopathogenic nematodes and the host immune response","volume":"37","author":"Li X. 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Immunol."},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.ibmb.2005.02.017","article-title":"Insect renal tubules constitute a cell-autonomous immune system that protects the organism against bacterial infection","volume":"35","author":"McGettigan J.","year":"2005","unstructured":"J. McGettigan ., Insect renal tubules constitute a cell-autonomous immune system that protects the organism against bacterial infection. Insect Biochem. Mol. Biol. 35, 741\u2013754 (2005).","journal-title":"Insect Biochem. Mol. Biol."},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"e40714","DOI":"10.1371\/annotation\/4b02305d-dcb8-40db-8f1f-1f7f0da51544","article-title":"Immune response and anti-microbial peptides expression in Malpighian tubules of Drosophila melanogaster is under developmental regulation","volume":"7","author":"Verma P.","year":"2012","unstructured":"P. Verma, M. G. Tapadia, Immune response and anti-microbial peptides expression in Malpighian tubules of Drosophila melanogaster is under developmental regulation. PLoS One 7, e40714 (2012).","journal-title":"PLoS One"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12915-018-0532-5","article-title":"Dehydration triggers ecdysone-mediated recognition-protein priming and elevated anti-bacterial immune responses in Drosophila Malpighian tubule renal cells","volume":"16","author":"Zheng W.","year":"2018","unstructured":"W. Zheng ., Dehydration triggers ecdysone-mediated recognition-protein priming and elevated anti-bacterial immune responses in Drosophila Malpighian tubule renal cells. BMC Biol. 16, 60 (2018).","journal-title":"BMC Biol."},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nri3763","article-title":"Immunity in Drosophila melanogaster\u2014From microbial recognition to whole-organism physiology","volume":"14","author":"Buchon N.","year":"2014","unstructured":"N. Buchon, N. Silverman, S. Cherry, Immunity in Drosophila melanogaster\u2014From microbial recognition to whole-organism physiology. Nat. Rev. Immunol. 14, 796\u2013810 (2014).","journal-title":"Nat. Rev. Immunol."},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ygcen.2008.09.012","article-title":"Modulation of epithelial innate immunity by autocrine production of nitric oxide","volume":"162","author":"Davies S. A.","year":"2009","unstructured":"S. A. Davies, J. A. Dow, Modulation of epithelial innate immunity by autocrine production of nitric oxide. Gen. Comp. 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Miura, Persephone\/Sp\u00e4tzle pathogen sensors mediate the activation of Toll receptor signaling in response to endogenous danger signals in apoptosis-deficient Drosophila. J. Biol. Chem. 289, 7558\u20137568 (2014).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"eaal1505","DOI":"10.1126\/sciimmunol.aal1505","article-title":"Activation of mosquito complement antiplasmodial response requires cellular immunity","volume":"2","author":"Castillo J. C.","year":"2017","unstructured":"J. C. Castillo, A. B. B. Ferreira, N. Trisnadi, C. Barillas-Mury, Activation of mosquito complement antiplasmodial response requires cellular immunity. Sci. Immunol. 2, eaal1505 (2017).","journal-title":"Sci. Immunol."},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.immuni.2006.08.019","article-title":"Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei","volume":"25","author":"Frolet C.","year":"2006","unstructured":"C. Frolet, M. Thoma, S. Blandin, J. A. Hoffmann, E. A. Levashina, Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei. Immunity 25, 677\u2013685 (2006).","journal-title":"Immunity"},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"e1000098","DOI":"10.1371\/journal.ppat.1000098","article-title":"The Aedes aegypti toll pathway controls dengue virus infection","volume":"4","author":"Xi Z.","year":"2008","unstructured":"Z. Xi, J. L. Ramirez, G. Dimopoulos, The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog. 4, e1000098 (2008).","journal-title":"PLoS Pathog."},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","first-page":"E111","DOI":"10.3390\/ijerph14020111","article-title":"Malpighian tubules as novel targets for mosquito control","volume":"14","author":"Piermarini P. M.","year":"2017","unstructured":"P. M. Piermarini, C. J. Esquivel, J. S. Denton, Malpighian tubules as novel targets for mosquito control. Int. J. Environ. Res. Public Health 14, E111 (2017).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.aak9691","article-title":"Changes in the microbiota cause genetically modified Anopheles to spread in a population","volume":"357","author":"Pike A.","year":"2017","unstructured":"A. Pike ., Changes in the microbiota cause genetically modified Anopheles to spread in a population. Science 357, 1396\u20131399 (2017).","journal-title":"Science"},{"key":"e_1_3_4_51_2","doi-asserted-by":"crossref","first-page":"e1002458","DOI":"10.1371\/journal.ppat.1002458","article-title":"Engineered Anopheles immunity to Plasmodium infection","volume":"7","author":"Dong Y.","year":"2011","unstructured":"Y. Dong ., Engineered Anopheles immunity to Plasmodium infection. PLoS Pathog. 7, e1002458 (2011).","journal-title":"PLoS Pathog."},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s00251-019-01119-8","article-title":"Transcript analysis reveals the involvement of NF-\u03baB transcription factors for the activation of TGF-\u03b2 signaling in nematode-infected Drosophila","volume":"71","author":"Patrnogic J.","year":"2019","unstructured":"J. Patrnogic, C. Heryanto, Y. Ozakman, I. Eleftherianos, Transcript analysis reveals the involvement of NF-\u03baB transcription factors for the activation of TGF-\u03b2 signaling in nematode-infected Drosophila. Immunogenetics 71, 501\u2013510 (2019).","journal-title":"Immunogenetics"},{"key":"e_1_3_4_53_2","first-page":"61","article-title":"Studies on filariasis X: A trial to analyze refractory mechanisms of the mosquito Aedes aegypti to the filarial larvae Brugia malayi by means of parabiotic twinning","volume":"13","author":"Kobayashi M.","year":"1986","unstructured":"M. Kobayashi, N. Ogura, H. Yamamoto, Studies on filariasis X: A trial to analyze refractory mechanisms of the mosquito Aedes aegypti to the filarial larvae Brugia malayi by means of parabiotic twinning. Dokkyo J. Med. Sci. 13, 61\u201367 (1986).","journal-title":"Dokkyo J. Med. Sci."},{"key":"e_1_3_4_54_2","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1073\/pnas.1000251107","article-title":"Female-specific flightless phenotype for mosquito control","volume":"107","author":"Fu G.","year":"2010","unstructured":"G. Fu ., Female-specific flightless phenotype for mosquito control. Proc. Natl. Acad. Sci. U.S.A. 107, 4550\u20134554 (2010).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_55_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3389\/fphys.2017.00283","article-title":"RNA-seq comparison of larval and adult Malpighian tubules of the yellow Fever mosquito Aedes aegypti reveals life stage-specific changes in renal function","volume":"8","author":"Li Y.","year":"2017","unstructured":"Y. Li ., RNA-seq comparison of larval and adult Malpighian tubules of the yellow Fever mosquito Aedes aegypti reveals life stage-specific changes in renal function. Front. Physiol. 8, 283 (2017).","journal-title":"Front. Physiol."},{"key":"e_1_3_4_56_2","doi-asserted-by":"crossref","first-page":"e88398","DOI":"10.1371\/journal.pone.0088398","article-title":"Differential induction of TLR3-dependent innate immune signaling by closely related parasite species","volume":"9","author":"Beiting D. P.","year":"2014","unstructured":"D. P. Beiting ., Differential induction of TLR3-dependent innate immune signaling by closely related parasite species. PLoS One 9, e88398 (2014).","journal-title":"PLoS One"},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","article-title":"Bioconductor: Open software development for computational biology and bioinformatics","volume":"5","author":"Gentleman R. C.","year":"2004","unstructured":"R. C. Gentleman ., Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol. 5, R80 (2004).","journal-title":"Genome Biol."},{"key":"e_1_3_4_58_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nmeth.3252","article-title":"Orchestrating high-throughput genomic analysis with bioconductor","volume":"12","author":"Huber W.","year":"2015","unstructured":"W. Huber ., Orchestrating high-throughput genomic analysis with bioconductor. Nat. Methods 12, 115\u2013121 (2015).","journal-title":"Nat. Methods"},{"key":"e_1_3_4_59_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray N. L.","year":"2016","unstructured":"N. L. Bray, H. Pimentel, P. Melsted, L. Pachter, Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol. 34, 525\u2013527 (2016).","journal-title":"Nat. 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