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This study reveals that host-derived tumor necrosis factor \u03b1 (TNF-\u03b1) binds to the mosquito receptor Wengen (Wgn), promoting the transmission of both rodent and human malaria. This TNF-\u03b1\/Wgn signaling acts through mosquito TNF receptor-associated factor 3 (mTRAF3), which inhibits mosquito immune deficiency (IMD) pathway-related molecules by targeting transforming growth factor-\u03b2-activated kinase 1 (mTAK1), leading to decreased thioester-containing protein 1 (TEP1) production and increased parasite infection in mosquitoes. Additionally, neutralizing host-derived TNF-\u03b1 by an anti-TNF-\u03b1 antibody prevents experimental cerebral malaria (ECM) and enhances the effectiveness of an anti-Pfs25 antibody in blocking transmission. Our findings uncover a novel strategy by which host-derived TNF-\u03b1 can be utilized by the parasite to facilitate its transmission, offering new avenues for preventing cerebral malaria and reducing malaria transmission.<\/jats:p>","DOI":"10.1038\/s44319-026-00929-8","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:20:56Z","timestamp":1790702456000},"page":"6191-6222","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-species TNF-\u03b1 signaling in mosquitoes promotes malaria transmission"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5253-5562","authenticated-orcid":false,"given":"Meilin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6371-6782","authenticated-orcid":false,"given":"Biao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongling","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoli","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanli","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3681-5052","authenticated-orcid":false,"given":"Wenyue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"929_CR1","doi-asserted-by":"publisher","first-page":"e00775","DOI":"10.1128\/IAI.00775-18","volume":"87","author":"FK Acquah","year":"2019","unstructured":"Acquah FK, Adjah J, Williamson KC, Amoah LE (2019) Transmission-blocking vaccines: old friends and new prospects. 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