Rapamycin inhibits pathogen transmission in mosquitoes by promoting immune activation.

Abstract

Repeated blood meals provide essential nutrients for mosquito egg development and routes for pathogen transmission. The target of rapamycin, the TOR pathway, is essential for vitellogenesis. However, its influence on pathogen transmission remains to be elucidated. Here, we show that rapamycin, an inhibitor of the TOR pathway, effectively suppresses Plasmodium berghei infection in Anopheles stephensi. An. stephensi injected with rapamycin or feeding on rapamycin-treated mice showed increased resistance to P. berghei infection. Exposing An. stephensi to a rapamycin-coated surface not only decreased the numbers of both oocysts and sporozoites but also impaired mosquito survival and fecundity. Transcriptome analysis revealed that the inhibitory effect of rapamycin on parasite infection was through the enhanced activation of immune responses, especially the NF-κB transcription factor REL2, a regulator of the immune pathway and complement system. Knockdown of REL2 in rapamycin-treated mosquitoes abrogated the induction of the complement-like proteins TEP1 and SPCLIP1 and abolished rapamycin-mediated refractoriness to Plasmodium infection. Together, these findings demonstrate a key role of the TOR pathway in regulating mosquito immune responses, thereby influencing vector competence.

• Authors: Yuebiao Feng, Lu Chen, Li Gao, Li Dong, Han Wen, Xiumei Song, Fang Luo, Gong Cheng, Jingwen Wang
• Journal: PLoS pathogens (PLoS Pathog) Vol. 17 Issue 2 Pg. e1009353 (02 2021) ISSN: 1553-7374 [Electronic] United States
• PMID: 33626094 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Sirolimus

Topics

• Animals
• Anopheles (drug effects, immunology, parasitology)
• Female
• Gene Expression Profiling
• Immunity, Innate (drug effects, immunology)
• Immunosuppressive Agents (pharmacology)
• Malaria (drug therapy, immunology, parasitology, transmission)
• Mice
• Mice, Inbred BALB C
• Mosquito Vectors (drug effects, immunology, parasitology)
• Oocysts (drug effects, growth & development, immunology)
• Plasmodium berghei (pathogenicity)
• Sirolimus (pharmacology)
• Sporozoites (drug effects, growth & development, immunology)