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To explore the immune consequences of this chronic vector exposure, we performed a human challenge study with the sand fly\n                    <jats:italic>Lutzomyia longipalpis<\/jats:italic>\n                    . Peripheral blood mononuclear cells were collected from fifteen healthy volunteers who underwent multiple controlled exposures to sand fly bites. We identified two\n                    <jats:italic>Lu. longipalpis<\/jats:italic>\n                    salivary proteins, LJM19 and LJL143, which elicit type 1 cytokine responses in cells from exposed individuals and which correlate with enhanced killing of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    parasites in co-cultured macrophages. Interestingly, LJM19 also exerts this parasite-killing effect in cells from unexposed individuals, consistent with innate immune activation. In support of this, both LJM19 and LJL143 stimulate the production of the innate cytokines IL-1\u03b2 and IFN-\u03b1. Our results demonstrate that repeated exposure to sand fly bites induces innate and adaptive cytokine responses to vector salivary proteins that can be co-opted to protect humans against\n                    <jats:italic>Leishmania<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.1038\/s42003-026-10130-1","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:36:12Z","timestamp":1778002572000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human sand fly challenge elicits saliva-specific innate and type 1-polarized immunity that promotes Leishmania killing"],"prefix":"10.1038","volume":"9","author":[{"given":"Maha","family":"Abdeladhim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roseanne","family":"Ressner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Hummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0069-7867","authenticated-orcid":false,"given":"Ranadhir","family":"Dey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regis","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldion\u00ea","family":"de Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Fortes","family":"de Araujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George W.","family":"Turiansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Iniguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Meneses","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-8038","authenticated-orcid":false,"given":"Fabiano","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Aronson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9956-8039","authenticated-orcid":false,"given":"Joshua R.","family":"Lacsina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-9450","authenticated-orcid":false,"given":"Jesus G.","family":"Valenzuela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-636X","authenticated-orcid":false,"given":"Shaden","family":"Kamhawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"10130_CR1","unstructured":"Global Burden of Disease Collaborative Network. 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