{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:28:54Z","timestamp":1790749734528,"version":"4.1.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"the State Key Program of The National Natural Science Foundation of China","award":["81830067"],"award-info":[{"award-number":["81830067"]}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302570"],"award-info":[{"award-number":["82302570"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372287"],"award-info":[{"award-number":["82372287"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:p>\n                    Host-derived factors ingested during mosquito blood feeding are poorly understood modulators of malaria transmission. Here, we demonstrated that host complement C3, acquired by mosquitoes during\n                    <jats:italic toggle=\"yes\">Plasmodium<\/jats:italic>\n                    infection, significantly enhanced rodent malaria infection in laboratory-reared mosquitoes. This effect was recapitulated in field-caught\n                    <jats:italic toggle=\"yes\">Anopheles sinensis<\/jats:italic>\n                    mosquitoes, confirming its relevance to malaria transmission in a more natural setting. Moreover, host-derived C3 significantly reduced the efficacy of anti-Pfs25 antibodies in blocking malaria transmission. Mechanistically, host-derived C3 lyses the mosquito midgut symbiont\n                    <jats:italic toggle=\"yes\">Elizabethkingia anophelis<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">E. anophelis<\/jats:italic>\n                    )\u2014a bacterium that intrinsically suppresses parasite development by blocking the zygote-to-ookinete transition. Strikingly, host-derived C3 in mosquitoes appears to be activated by the alternative pathway, and inhibiting Factor B with Iptacopan (LNP023) reduced\n                    <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                    ) infection, while increased the efficacy of anti-Pfs25 antibodies to blocking\n                    <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                    transmission in the standard membrane-feeding assay. Therefore, this study describes a strategy of the malaria parasite to utilize host complement C3 to promote its transmission and provides us with an avenue to block malaria transmission and improve the blocking efficacy of anti-Pfs25 antibodies by the inhibition of C3 activation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2424570122","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T11:06:42Z","timestamp":1748430402000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Host complement C3 promotes malaria transmission by killing symbiotic bacteria in the mosquito midgut"],"prefix":"10.1073","volume":"122","author":[{"given":"Biao","family":"He","sequence":"first","affiliation":[{"name":"Department of Pathogenic Biology, Army Medical University","place":["Chongqing, 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Exp."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2424570122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T11:07:07Z","timestamp":1748430427000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2424570122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":48,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2025,6,3]]}},"alternative-id":["10.1073\/pnas.2424570122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2424570122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,28]]},"assertion":[{"value":"2024-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2424570122"}}