Cross-species TNF-α signaling in mosquitoes promotes malaria transmission
- 1Department of Pathogenic Biology, Army Medical University (Third Military Medical University), Chongqing, China
- 2Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China
Abstract
The interactions between innate immune responses in mammals and insects on vector-borne disease transmission are poorly understood. This study reveals that host-derived tumor necrosis factor α (TNF-α) binds to the mosquito receptor Wengen (Wgn), promoting the transmission of both rodent and human malaria. This TNF-α/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-β-activated kinase 1 (mTAK1), leading to decreased thioester-containing protein 1 (TEP1) production and increased parasite infection in mosquitoes. Additionally, neutralizing host-derived TNF-α by an anti-TNF-α 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-α can be utilized by the parasite to facilitate its transmission, offering new avenues for preventing cerebral malaria and reducing malaria transmission.
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BibTeX
@article{li2026crossspecies,
title = {{Cross-species TNF-α signaling in mosquitoes promotes malaria transmission}},
author = {Meilin Li and Biao He and Jian Zhang and Yongling Fan and Jianyong Li and Feng Zhu and Shuai Guo and Taoli Zhou and Yuanli Gao and Taiping Liu and Wenyue Xu},
journal = {EMBO Reports},
year = {2026},
month = sep,
doi = {10.1038/s44319-026-00929-8},
url = {https://doi.org/10.1038/s44319-026-00929-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cross-species TNF-α signaling in mosquitoes promotes malaria transmission
AU - Meilin Li
AU - Biao He
AU - Jian Zhang
AU - Yongling Fan
AU - Jianyong Li
AU - Feng Zhu
AU - Shuai Guo
AU - Taoli Zhou
AU - Yuanli Gao
AU - Taiping Liu
AU - Wenyue Xu
PY - 2026
DA - 2026/09/29
JO - EMBO Reports
DO - 10.1038/s44319-026-00929-8
UR - https://doi.org/10.1038/s44319-026-00929-8
AB - The interactions between innate immune responses in mammals and insects on vector-borne disease transmission are poorly understood. This study reveals that host-derived tumor necrosis factor α (TNF-α) binds to the mosquito receptor Wengen (Wgn), promoting the transmission of both rodent and human malaria. This TNF-α/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-β-activated kinase 1 (mTAK1), leading to decreased thioester-containing protein 1 (TEP1) production and increased parasite infection in mosquitoes. Additionally, neutralizing host-derived TNF-α by an anti-TNF-α 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-α can be utilized by the parasite to facilitate its transmission, offering new avenues for preventing cerebral malaria and reducing malaria transmission.
SN - 1469-221X
SN - 1469-3178
ER -