{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:01:58Z","timestamp":1777532518313,"version":"3.51.4"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Human body lice, <jats:italic>Pediculus humanus humanus<\/jats:italic>, are blood-feeding parasites that live in clothing and feed several times per day. Saliva injected during louse feeding induces pruritis and local inflammation in the skin. If untreated, chronic Pediculosis can cause systemic negative health effects. Despite the medical importance of body lice and their longstanding association with humans, characterization of their saliva has been limited. To address this, we extracted RNA and protein from two of the body louse\u2019s morphologically distinct sets of salivary glands (Bean-shaped and U-shaped) and generated transcript and protein profiles for each. Additionally, we performed fluorescent staining and confocal microscopy on each gland type to enhance descriptions of their structure and gross cellular architecture. Analysis of body louse salivary gene products and proteins revealed that the overwhelming majority were not closely related to biomolecules of known function, highlighting the organism\u2019s unique and understudied saliva composition. Despite the contrasting morphology of the two gland types, there was a high degree of overlap in the salivary products produced. This finding suggests strong Darwinian selection pressure to maintain both salivary gland types, given that it would be simpler to have a single morphologically identical set of glands. Here we present the first next-generation sequencing and proteomic characterization of the human body louse sialome, discuss the potential physiological importance of louse salivary proteins, and consider possible explanations for why lice have a complex salivary gland system despite inordinate redundancy in the protein repertoire of the Bean- and U-shaped salivary glands.<\/jats:p>","DOI":"10.1038\/s41598-025-01412-5","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T08:28:17Z","timestamp":1748248097000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An insight into the salivary gland content of the human body louse, Pediculus humanus"],"prefix":"10.1038","volume":"15","author":[{"given":"David M.","family":"Bland","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sazzad","family":"Mahmood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M. C.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"1412_CR1","volume-title":"Arthropods as Vectors of Emerging Diseases","author":"GA Schaub","year":"2012","unstructured":"Schaub, G. A., Kollien, A. H. & Blalczun, C. Lice as vectors of bacterial diseases. In Arthropods as Vectors of Emerging Diseases (ed. Mehlhorn, H.) (Springer, 2012)."},{"issue":"2","key":"1412_CR2","doi-asserted-by":"publisher","first-page":"e17","DOI":"10.1016\/S1473-3099(20)30487-4","volume":"21","author":"R Barbieri","year":"2021","unstructured":"Barbieri, R., Drancourt, M. & Raoult, D. The role of louse-transmitted diseases in historical plague pandemics. Lancet Infect. Dis. 21(2), e17\u2013e25 (2021).","journal-title":"Lancet Infect. Dis."},{"issue":"11","key":"1412_CR3","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.3201\/eid2311.170516","volume":"23","author":"TDA Ly","year":"2017","unstructured":"Ly, T. D. A. et al. Changing demographics and prevalence of body lice among homeless persons, Marseille, France. Emerg. Infect. Dis. 23(11), 1894\u20131897 (2017).","journal-title":"Emerg. Infect. Dis."},{"issue":"10","key":"1412_CR4","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.3201\/eid2010.131655","volume":"20","author":"DL Bonilla","year":"2014","unstructured":"Bonilla, D. L. et al. Risk factors for human lice and bartonellosis among the homeless, San Francisco, California, USA. Emerg. Infect. Dis. 20(10), 1645\u20131651 (2014).","journal-title":"Emerg. Infect. Dis."},{"issue":"3","key":"1412_CR5","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1086\/499279","volume":"193","author":"C Foucault","year":"2006","unstructured":"Foucault, C. et al. Oral ivermectin in the treatment of body lice. J. Infect. Dis. 193(3), 474\u2013476 (2006).","journal-title":"J. Infect. Dis."},{"issue":"4","key":"1412_CR6","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1086\/520454","volume":"29","author":"D Raoult","year":"1999","unstructured":"Raoult, D. & Roux, V. The body louse as a vector of reemerging human diseases. Clin. Infect. Dis. 29(4), 888\u2013911 (1999).","journal-title":"Clin. Infect. Dis."},{"key":"1412_CR7","first-page":"1","volume":"55","author":"JW Maunder","year":"1983","unstructured":"Maunder, J. W. The appreciation of lice. Proc. R. Inst. Great Britain 55, 1\u201331 (1983).","journal-title":"Proc. R. Inst. Great Britain"},{"key":"1412_CR8","volume-title":"The Louse: An Account of the Lice Which Infest Man, Their Medical Importance and Control","author":"PA Buxton","year":"1939","unstructured":"Buxton, P. A. The Louse: An Account of the Lice Which Infest Man, Their Medical Importance and Control (Edward Arnold & Co., 1939)."},{"key":"1412_CR9","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S0065-308X(08)60493-5","volume":"36","author":"IF Burgess","year":"1995","unstructured":"Burgess, I. F. Human lice and their management. Adv. Parasitol. 36, 271\u2013342 (1995).","journal-title":"Adv. Parasitol."},{"issue":"12","key":"1412_CR10","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.pt.2012.09.003","volume":"28","author":"A Veracx","year":"2012","unstructured":"Veracx, A. & Raoult, D. Biology and genetics of human head and body lice. Trends Parasitol. 28(12), 563\u2013571 (2012).","journal-title":"Trends Parasitol."},{"issue":"5","key":"1412_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002625","volume":"22","author":"DM Bland","year":"2024","unstructured":"Bland, D. M. et al. Yersinia pestis can infect the Pawlowsky glands of human body lice and be transmitted by louse bite. PLoS Biol. 22(5), e3002625 (2024).","journal-title":"PLoS Biol."},{"issue":"6","key":"1412_CR12","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1001\/jamadermatol.2022.0818","volume":"158","author":"N Rudd","year":"2022","unstructured":"Rudd, N. et al. Association of body lice infestation with hemoglobin values in hospitalized dermatology patients. JAMA Dermatol. 158(6), 691\u2013693 (2022).","journal-title":"JAMA Dermatol."},{"key":"1412_CR13","unstructured":"Bramlett, J., Wache, S. & Jones, D. Structure of salivary glands of the human body louse, Pediculus humanus L., and erythematous and immunogenic properties of its saliva. In Endocrine Interactions of Insect Parasites and Pathogens, 219\u2013232 (2001)."},{"issue":"1","key":"1412_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S0031182000010921","volume":"22","author":"D Keilin","year":"1930","unstructured":"Keilin, D. & Nuttall, G. H. F. Iconographic studies of Pediculus humanus. Parasitol 22(1), 1\u201310 (1930).","journal-title":"Parasitol"},{"key":"1412_CR15","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1017\/S0031182000004121","volume":"XI","author":"AD Peacock","year":"1918","unstructured":"Peacock, A. D. The structure of the mouthparts and mechanism of feeding in Pediculus humanus. Parasitol XI, 98\u2013117 (1918).","journal-title":"Parasitol"},{"issue":"11\u201312","key":"1412_CR16","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/S0022-1910(96)00059-5","volume":"42","author":"KY Mumcuoglu","year":"1996","unstructured":"Mumcuoglu, K. Y. et al. Antihemostatic activity in salivary glands of the human body louse, Pediculus humanus humanus (Anoplura: Pediculidae). J. Insect. Phys. 42(11\u201312), 1083\u20131087 (1996).","journal-title":"J. Insect. Phys."},{"issue":"2","key":"1412_CR17","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1111\/mve.12287","volume":"32","author":"AG De La Filia","year":"2018","unstructured":"De La Filia, A. G. et al. The unusual reproductive system of head and body lice (Pediculus humanus). Med. Vet. Entomol. 32(2), 226\u2013234 (2018).","journal-title":"Med. Vet. Entomol."},{"issue":"6","key":"1412_CR18","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1101\/gr.089532.108","volume":"19","author":"JT Simpson","year":"2009","unstructured":"Simpson, J. T. et al. ABySS: A parallel assembler for short read sequence data. Genome Res. 19(6), 1117\u20131123 (2009).","journal-title":"Genome Res."},{"issue":"7","key":"1412_CR19","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/nbt.1883","volume":"29","author":"MG Grabherr","year":"2011","unstructured":"Grabherr, M. G. et al. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat. Biotechnol. 29(7), 644\u2013652 (2011).","journal-title":"Nat. Biotechnol."},{"issue":"23","key":"1412_CR20","doi-asserted-by":"publisher","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","volume":"28","author":"L Fu","year":"2012","unstructured":"Fu, L. et al. CD-HIT: Accelerated for clustering the next-generation sequencing data. Bioinformatics 28(23), 3150\u20133152 (2012).","journal-title":"Bioinformatics"},{"issue":"4","key":"1412_CR21","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.jmb.2004.05.028","volume":"340","author":"JD Bendtsen","year":"2004","unstructured":"Bendtsen, J. D. et al. Improved prediction of signal peptides: SignalP 3.0. J. Mol. Biol. 340(4), 783\u2013795 (2004).","journal-title":"J. Mol. Biol."},{"issue":"27","key":"1412_CR22","doi-asserted-by":"publisher","first-page":"12168","DOI":"10.1073\/pnas.1003379107","volume":"107","author":"EF Kirkness","year":"2010","unstructured":"Kirkness, E. F. et al. Genome sequences of the human body louse and its primary endosymbiont provide insights into the permanent parasitic lifestyle. Proc. Natl. Acad. Sci. U.S.A. 107(27), 12168\u201312173 (2010).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"1412_CR23","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","volume":"12","author":"B Li","year":"2011","unstructured":"Li, B. & Dewey, C. N. RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform. 12, 323 (2011).","journal-title":"BMC Bioinform."},{"issue":"7873","key":"1412_CR24","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","volume":"596","author":"J Jumper","year":"2021","unstructured":"Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596(7873), 583\u2013589 (2021).","journal-title":"Nature"},{"key":"1412_CR25","volume-title":"R: A Language and Environment for Statistical Computing","author":"RC Team","year":"2021","unstructured":"Team, R. C. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2021)."},{"issue":"1","key":"1412_CR26","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nprot.2015.133","volume":"11","author":"PC Carvalho","year":"2016","unstructured":"Carvalho, P. C. et al. Integrated analysis of shotgun proteomic data with PatternLab for proteomics 4.0. Nat. Protoc. 11(1), 102\u2013117 (2016).","journal-title":"Nat. Protoc."},{"issue":"1","key":"1412_CR27","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1002\/pmic.201200439","volume":"13","author":"JK Eng","year":"2013","unstructured":"Eng, J. K., Jahan, T. A. & Hoopmann, M. R. Comet: An open-source MS\/MS sequence database search tool. Proteomics 13(1), 22\u201324 (2013).","journal-title":"Proteomics"},{"issue":"Suppl","key":"1412_CR28","doi-asserted-by":"publisher","first-page":"S67","DOI":"10.1017\/S0031182004006468","volume":"129","author":"AS Bowman","year":"2004","unstructured":"Bowman, A. S. & Sauer, J. R. Tick salivary glands: Function, physiology and future. Parasitology 129(Suppl), S67-81 (2004).","journal-title":"Parasitology"},{"key":"1412_CR29","first-page":"59","volume":"1858","author":"RM Waterhouse","year":"2019","unstructured":"Waterhouse, R. M. et al. Using BUSCO to assess insect genomic resources. Insect Genomics 1858, 59\u201374 (2019).","journal-title":"Insect Genomics"},{"key":"1412_CR30","doi-asserted-by":"publisher","first-page":"103899","DOI":"10.1016\/j.jprot.2020.103899","volume":"229","author":"L Tirloni","year":"2020","unstructured":"Tirloni, L. et al. Integrated analysis of sialotranscriptome and sialoproteome of the brown dog tick Rhipicephalus sanguineus (s.l.): Insights into gene expression during blood feeding. J. Proteomics 229, 103899 (2020).","journal-title":"J. Proteomics"},{"issue":"1","key":"1412_CR31","doi-asserted-by":"publisher","first-page":"e0279070","DOI":"10.1371\/journal.pone.0279070","volume":"18","author":"SP Lu","year":"2023","unstructured":"Lu, S. P. et al. Revisiting the sialome of the cat flea Ctenocephalides felis. PLoS ONE 18(1), e0279070 (2023).","journal-title":"PLoS ONE"},{"issue":"3","key":"1412_CR32","doi-asserted-by":"publisher","first-page":"499","DOI":"10.4269\/ajtmh.1948.s1-28.499","volume":"28","author":"GH Culpepper","year":"1948","unstructured":"Culpepper, G. H. Rearing and maintaining a laboratory colony of body lice on rabbits. Am. J. Trop. Med. Hyg. 28(3), 499\u2013504 (1948).","journal-title":"Am. J. Trop. Med. Hyg."},{"issue":"3","key":"1412_CR33","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.pestbp.2006.04.001","volume":"86","author":"KS Yoon","year":"2006","unstructured":"Yoon, K. S. et al. An improved in vitro rearing system for the human head louse allows the determination of resistance to formulated pediculicides. Pestic. Biochem. Phys. 86(3), 195\u2013202 (2006).","journal-title":"Pestic. Biochem. Phys."},{"key":"1412_CR34","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3389\/fcimb.2017.00517","volume":"7","author":"L Tirloni","year":"2017","unstructured":"Tirloni, L. et al. Tick-host range adaptation: Changes in protein profiles in unfed adult Ixodes scapularis and Amblyomma americanum saliva stimulated to feed on different hosts. Front. Cell. Infect. Microbiol. 7, 517 (2017).","journal-title":"Front. Cell. Infect. Microbiol."},{"issue":"10","key":"1412_CR35","doi-asserted-by":"publisher","first-page":"3728","DOI":"10.1073\/pnas.0813190106","volume":"106","author":"E Calvo","year":"2009","unstructured":"Calvo, E. et al. Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein. Proc. Natl. Acad. Sci. U.S.A. 106(10), 3728\u20133733 (2009).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"7","key":"1412_CR36","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1021\/acschembio.6b00032","volume":"11","author":"W Jablonka","year":"2016","unstructured":"Jablonka, W. et al. Structure and ligand-binding mechanism of a cysteinyl leukotriene-binding protein from a blood-feeding disease vector. ACS Chem. Biol. 11(7), 1934\u20131944 (2016).","journal-title":"ACS Chem. Biol."},{"issue":"5","key":"1412_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101322","volume":"297","author":"S Lu","year":"2021","unstructured":"Lu, S. et al. Identification of a substrate-like cleavage-resistant thrombin inhibitor from the saliva of the flea Xenopsylla cheopis. J. Biol. Chem. 297(5), 101322 (2021).","journal-title":"J. Biol. Chem."},{"issue":"7","key":"1412_CR38","doi-asserted-by":"publisher","first-page":"e0131292","DOI":"10.1371\/journal.pone.0131292","volume":"10","author":"S Karim","year":"2015","unstructured":"Karim, S. & Ribeiro, J. M. C. An insight into the sialome of the lone star tick, Amblyomma americanum, with a glimpse on its time dependent gene expression. PLoS ONE 10(7), e0131292 (2015).","journal-title":"PLoS ONE"},{"issue":"7","key":"1412_CR39","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/S0965-1748(03)00067-5","volume":"33","author":"JG Valenzuela","year":"2003","unstructured":"Valenzuela, J. G. et al. Exploring the salivary gland transcriptome and proteome of the Anopheles stephensi mosquito. Insect Biochem. Mol. Biol. 33(7), 717\u2013732 (2003).","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"1","key":"1412_CR40","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s12864-023-09236-1","volume":"24","author":"S Lu","year":"2023","unstructured":"Lu, S. et al. A deeper insight into the sialome of male and female Culex quinquefasciatus mosquitoes. BMC Genomics 24(1), 135 (2023).","journal-title":"BMC Genomics"},{"key":"1412_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2021.104476","volume":"254","author":"S Lu","year":"2022","unstructured":"Lu, S. et al. Integrated analysis of the sialotranscriptome and sialoproteome of the rat flea Xenopsylla cheopis. J. Proteomics 254, 104476 (2022).","journal-title":"J. Proteomics"},{"issue":"2","key":"1412_CR42","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.ibmb.2007.11.001","volume":"38","author":"TC Assumpcao","year":"2008","unstructured":"Assumpcao, T. C. et al. An insight into the sialome of the blood-sucking bug Triatoma infestans, a vector of Chagas\u2019 disease. Insect Biochem. Mol. Biol. 38(2), 213\u2013232 (2008).","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"2","key":"1412_CR43","doi-asserted-by":"publisher","first-page":"e0006243","DOI":"10.1371\/journal.pntd.0006243","volume":"12","author":"JC Nevoa","year":"2018","unstructured":"Nevoa, J. C. et al. An insight into the salivary gland and fat body transcriptome of Panstrongylus lignarius (Hemiptera: Heteroptera), the main vector of Chagas disease in Peru. PLoS Negl. Trop. Dis. 12(2), e0006243 (2018).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"1412_CR44","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S0065-2806(09)37002-2","volume":"37","author":"JMC Ribeiro","year":"2009","unstructured":"Ribeiro, J. M. C. & Arc\u00e0, B. From sialomes to the sialoverse: An insight into salivary potion of blood-feeding insects. Adv. Insect Physiol. 37, 59 (2009).","journal-title":"Adv. Insect Physiol."},{"issue":"4\u20135","key":"1412_CR45","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/S0965-1748(00)00151-X","volume":"31","author":"R Amino","year":"2001","unstructured":"Amino, R., Tanaka, A. S. & Schenkman, S. Triapsin, an unusual activatable serine protease from the saliva of the hematophagous vector of Chagas\u2019 disease Triatoma infestans (Hemiptera: Reduviidae). Insect Biochem. Mol. Biol. 31(4\u20135), 465\u2013472 (2001).","journal-title":"Insect Biochem. Mol. Biol."},{"key":"1412_CR46","doi-asserted-by":"publisher","DOI":"10.1590\/1678-9199-jvatitd-2020-0098","volume":"27","author":"KA Oliveira","year":"2021","unstructured":"Oliveira, K. A. et al. Proteolytic activity of Triatoma infestans saliva associated with PAR-2 activation and vasodilation. J. Venom. Anim. Toxins Incl. Trop. Dis. 27, e20200098 (2021).","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"1412_CR47","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.toxicon.2013.10.025","volume":"77","author":"S Pichu","year":"2014","unstructured":"Pichu, S. et al. Purification of a serine protease and evidence for a protein C activator from the saliva of the tick, Ixodes scapularis. Toxicon 77, 32\u201339 (2014).","journal-title":"Toxicon"},{"issue":"D1","key":"1412_CR48","doi-asserted-by":"publisher","first-page":"D624","DOI":"10.1093\/nar\/gkx1134","volume":"46","author":"ND Rawlings","year":"2018","unstructured":"Rawlings, N. D. et al. The database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database. Nucleic Acids Res 46(D1), D624\u2013D632 (2018).","journal-title":"Nucleic Acids Res"},{"key":"1412_CR49","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3389\/fcimb.2017.00216","volume":"7","author":"J Chmelar","year":"2017","unstructured":"Chmelar, J. et al. Protease inhibitors in tick saliva: The role of serpins and cystatins in tick-host-pathogen interaction. Front. Cell. Infect. Microbiol. 7, 216 (2017).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"1412_CR50","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.3389\/fimmu.2018.01245","volume":"9","author":"T Sun","year":"2018","unstructured":"Sun, T. et al. An immunosuppressive tick salivary gland protein DsCystatin interferes with toll-like receptor signaling by downregulating TRAF6. Front. Immunol. 9, 1245 (2018).","journal-title":"Front. Immunol."},{"issue":"36","key":"1412_CR51","doi-asserted-by":"publisher","first-page":"26298","DOI":"10.1074\/jbc.M513010200","volume":"281","author":"M Kotsyfakis","year":"2006","unstructured":"Kotsyfakis, M. et al. Antiinflammatory and immunosuppressive activity of sialostatin L, a salivary cystatin from the tick. J. Biol. Chem. 281(36), 26298\u201326307 (2006).","journal-title":"J. Biol. Chem."},{"issue":"4","key":"1412_CR52","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1016\/j.bbrc.2005.07.036","volume":"334","author":"S Karim","year":"2005","unstructured":"Karim, S. et al. RNAi-mediated gene silencing to assess the role of synaptobrevin and cystatin in tick blood feeding. Biochem. Biophys. Res. Commun. 334(4), 1336\u20131342 (2005).","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"33","key":"1412_CR53","doi-asserted-by":"publisher","first-page":"20802","DOI":"10.1074\/jbc.273.33.20802","volume":"273","author":"KR Kenneth","year":"1998","unstructured":"Kenneth, K. R. & James, A. A. Isolation and characterization of the gene encoding a novel factor Xa-directed anticoagulant from the yellow fever mosquito. J. Biol. Chem. 273(33), 20802\u201320809 (1998).","journal-title":"J. Biol. Chem."},{"issue":"32","key":"1412_CR54","doi-asserted-by":"publisher","first-page":"27998","DOI":"10.1074\/jbc.M111.247924","volume":"286","author":"E Calvo","year":"2011","unstructured":"Calvo, E. et al. Alboserpin, a Factor Xa Inhibitor from the Mosquito vector of yellow fever, binds heparin and membrane phospholipids and exhibits antithrombotic activity. J. Biol. Chem. 286(32), 27998\u201328010 (2011).","journal-title":"J. Biol. Chem."},{"issue":"8","key":"1412_CR55","doi-asserted-by":"publisher","first-page":"e0007660","DOI":"10.1371\/journal.pntd.0007660","volume":"13","author":"L Tirloni","year":"2019","unstructured":"Tirloni, L. et al. serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding. PLoS Negl. Trop. Dis. 13(8), e0007660 (2019).","journal-title":"PLoS Negl. Trop. Dis."},{"issue":"4","key":"1412_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2020.101425","volume":"11","author":"ML Coutinho","year":"2020","unstructured":"Coutinho, M. L. et al. Rhipicephalus microplus serpins interfere with host immune responses by specifically modulating mast cells and lymphocytes. Ticks Tick Borne Dis. 11(4), 101425 (2020).","journal-title":"Ticks Tick Borne Dis."},{"issue":"1","key":"1412_CR57","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1111\/imm.13130","volume":"159","author":"F Wang","year":"2020","unstructured":"Wang, F. et al. The immunosuppressive functions of two novel tick serpins, HlSerpin-a and HlSerpin-b, from Haemaphysalis longicornis. Immunology 159(1), 109\u2013120 (2020).","journal-title":"Immunology"},{"issue":"17","key":"1412_CR58","doi-asserted-by":"publisher","first-page":"9480","DOI":"10.3390\/ijms22179480","volume":"22","author":"J Kotal","year":"2021","unstructured":"Kotal, J. et al. Ixodes ricinus salivary serpin iripin-8 inhibits the intrinsic pathway of coagulation and complement. Int. J. Mol. Sci. 22(17), 9480 (2021).","journal-title":"Int. J. Mol. Sci."},{"issue":"13","key":"1412_CR59","doi-asserted-by":"publisher","first-page":"6682","DOI":"10.1073\/pnas.94.13.6682","volume":"94","author":"ZC Liang","year":"1997","unstructured":"Liang, Z. C. et al. Pacifastin, a novel 155-kDa heterodimeric proteinase inhibitor containing a unique transferrin chain. Proc. Natl. Acad. Sci. U.S.A. 94(13), 6682\u20136687 (1997).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"3","key":"1412_CR60","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.peptides.2008.07.026","volume":"30","author":"B Breugelmans","year":"2009","unstructured":"Breugelmans, B. et al. Pacifastin-related peptides: Structural and functional characteristics of a family of serine peptidase inhibitors. Peptides 30(3), 622\u2013632 (2009).","journal-title":"Peptides"},{"issue":"7","key":"1412_CR61","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1016\/j.peptides.2010.03.033","volume":"31","author":"R de Marco","year":"2010","unstructured":"de Marco, R. et al. The first pacifastin elastase inhibitor characterized from a blood sucking animal. Peptides 31(7), 1280\u20131286 (2010).","journal-title":"Peptides"},{"issue":"46","key":"1412_CR62","doi-asserted-by":"publisher","first-page":"33593","DOI":"10.1074\/jbc.M706113200","volume":"282","author":"H Liu","year":"2007","unstructured":"Liu, H. et al. Phenoloxidase is an important component of the defense against Aeromonas hydrophila infection in a crustacean, Pacifastacus leniusculus. J. Biol. Chem. 282(46), 33593 (2007).","journal-title":"J. Biol. Chem."},{"key":"1412_CR63","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1016\/j.ijbiomac.2020.04.088","volume":"156","author":"TK Kim","year":"2020","unstructured":"Kim, T. K. et al. Amblyomma americanum serpin 41 (AAS41) inhibits inflammation by targeting chymase and chymotrypsin. Int. J. Biol. Macromol. 156, 1007\u20131021 (2020).","journal-title":"Int. J. Biol. Macromol."},{"issue":"9","key":"1412_CR64","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1016\/j.bbamcr.2017.05.019","volume":"1864","author":"LH Wong","year":"2017","unstructured":"Wong, L. H. & Levine, T. P. Tubular lipid binding proteins (TULIPs) growing everywhere. Biochim. Biophys. Acta Mol. Cell Res. 1864(9), 1439\u20131449 (2017).","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"issue":"1","key":"1412_CR65","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/0896-6273(94)90150-3","volume":"12","author":"CW Pikielny","year":"1994","unstructured":"Pikielny, C. W. et al. Members of a family of Drosophila putative odorant-binding proteins are expressed in different subsets of olfactory hairs. Neuron 12(1), 35\u201349 (1994).","journal-title":"Neuron"},{"issue":"23","key":"1412_CR66","doi-asserted-by":"publisher","first-page":"16340","DOI":"10.1016\/S0021-9258(17)34013-9","volume":"269","author":"MP McKenna","year":"1994","unstructured":"McKenna, M. P. et al. Putative Drosophila pheromone-binding proteins expressed in a subregion of the olfactory system. J. Biol. Chem. 269(23), 16340\u201316347 (1994).","journal-title":"J. Biol. Chem."},{"issue":"6","key":"1412_CR67","doi-asserted-by":"publisher","first-page":"3496","DOI":"10.1074\/jbc.M807467200","volume":"284","author":"C Hamiaux","year":"2009","unstructured":"Hamiaux, C. et al. Crystal structure of Epiphyas postvittana takeout 1 with bound ubiquinone supports a role as ligand carriers for takeout proteins in insects. J. Biol. Chem. 284(6), 3496\u20133503 (2009).","journal-title":"J. Biol. Chem."},{"issue":"Pt 16","key":"1412_CR68","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1242\/jeb.205.16.2429","volume":"205","author":"IM Francischetti","year":"2002","unstructured":"Francischetti, I. M. et al. Toward a catalog for the transcripts and proteins (sialome) from the salivary gland of the malaria vector Anopheles gambiae. J. Exp. Biol. 205(Pt 16), 2429\u20132451 (2002).","journal-title":"J. Exp. Biol."},{"key":"1412_CR69","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2022.103800","volume":"147","author":"S Lu","year":"2022","unstructured":"Lu, S. et al. A deeper insight into the sialome of male and female Ochlerotatus triseriatus mosquitoes. Insect Biochem. Mol. Biol. 147, 103800 (2022).","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"3","key":"1412_CR70","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3390\/toxins12030175","volume":"12","author":"T Tadokoro","year":"2020","unstructured":"Tadokoro, T. et al. Cysteine-rich secretory proteins (CRISPs) from venomous snakes: An overview of the functional diversity in a large and underappreciated superfamily. Toxins 12(3), 175 (2020).","journal-title":"Toxins"},{"issue":"7","key":"1412_CR71","doi-asserted-by":"publisher","first-page":"2823","DOI":"10.4049\/jimmunol.150.7.2823","volume":"150","author":"G Lu","year":"1993","unstructured":"Lu, G. et al. Sequence analysis and antigenic cross-reactivity of a venom allergen, antigen 5, from hornets, wasps, and yellow jackets. J. Immunol. 150(7), 2823\u20132830 (1993).","journal-title":"J. Immunol."},{"issue":"4","key":"1412_CR72","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1002\/prot.1160","volume":"45","author":"A Henriksen","year":"2001","unstructured":"Henriksen, A. et al. Major venom allergen of yellow jackets, Ves v 5: Structural characterization of a pathogenesis-related protein superfamily. Proteins 45(4), 438\u2013448 (2001).","journal-title":"Proteins"},{"issue":"3","key":"1412_CR73","doi-asserted-by":"publisher","first-page":"e0151400","DOI":"10.1371\/journal.pone.0151400","volume":"11","author":"JMC Ribeiro","year":"2016","unstructured":"Ribeiro, J. M. C. et al. A deep insight into the sialome of male and female Aedes aegypti mosquitoes. PLoS ONE 11(3), e0151400 (2016).","journal-title":"PLoS ONE"},{"key":"1412_CR74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ibmb.2018.03.001","volume":"95","author":"JMC Ribeiro","year":"2018","unstructured":"Ribeiro, J. M. C. et al. A deep insight into the male and female sialotranscriptome of adult Culex tarsalis mosquitoes. Insect Biochem. Mol. Biol. 95, 1\u20139 (2018).","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"5","key":"1412_CR75","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.ibmb.2007.12.006","volume":"38","author":"E Calvo","year":"2008","unstructured":"Calvo, E., Pham, V. M. & Ribeiro, J. M. An insight into the sialotranscriptome of the non-blood feeding Toxorhynchites amboinensis mosquito. Insect Biochem. Mol. Biol. 38(5), 499\u2013507 (2008).","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"9","key":"1412_CR76","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1074\/mcp.M900186-MCP200","volume":"8","author":"DY Ma","year":"2009","unstructured":"Ma, D. Y. et al. Anti-thrombosis repertoire of blood-feeding horsefly salivary glands. Mol. Cell Proteomics 8(9), 2071\u20132079 (2009).","journal-title":"Mol. Cell Proteomics"},{"issue":"20","key":"1412_CR77","doi-asserted-by":"publisher","first-page":"14341","DOI":"10.1074\/jbc.M113.466995","volume":"288","author":"TCF Assumpcao","year":"2013","unstructured":"Assumpcao, T. C. F. et al. Salivary antigen-5\/CAP family members are Cu2+-dependent antioxidant enzymes that scavenge O(2)(-) and inhibit collagen-induced platelet aggregation and neutrophil oxidative burst. J. Biol. Chem. 288(20), 14341\u201314361 (2013).","journal-title":"J. Biol. Chem."},{"issue":"11","key":"1412_CR78","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020340","volume":"2","author":"DL Reed","year":"2004","unstructured":"Reed, D. L. et al. Genetic analysis of lice supports direct contact between modern and archaic humans. PLoS Biol. 2(11), e340 (2004).","journal-title":"PLoS Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-01412-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-01412-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-01412-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T10:01:48Z","timestamp":1748253708000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-01412-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1412"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-01412-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,26]]},"assertion":[{"value":"14 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18322"}}