Host macrophages/monocytes promote malaria transmission by modulating mosquito microbiota via SR-A-mediated phagocytosis.

Blood-stage malaria infection significantly increases the number of immune cells in the peripheral blood of vertebrate hosts, yet their roles in malaria transmission by mosquitoes remain poorly understood. In this study, we demonstrate that macrophages/monocytes-rather than neutrophils or NK/NKT cells-play a crucial role in enhancing malaria transmission to mosquitoes, both in rodent models and human. Mechanistically, these macrophages/monocytes that migrate into the mosquito midgut suppress the growth of transmission-blocking microbiota, including E. anophelis, S. sonnei, and K. oxytoca, primarily through non-opsonic phagocytosis mediated by scavenger receptor A (SR-A). Importantly, either the depletion of macrophages/monocytes or the use anti-SR-A neutralizing antibodies significantly enhances the transmission-blocking efficacy of anti-Pfs25 monoclonal antibodies by increasing the abundance of these bacteria. This combination approach can lead to the complete blockade of transmission of Pfs25-transgenic Plasmodium berghei (P. berghei-pfs25). These findings reveal a previously unrecognized mechanism that the parasite co-opts host immune cells to eliminate transmission-blocking bacteria, suggesting opportunities for using anti-SR-A antibodies to inhibit malaria transmission and improve the efficacy of anti-Pfs25 monoclonal antibodies.