Mast cell-derived IL-10 regulates malaria parasite transmission to Anopheles stephensi with a female-biased immune response

Malaria is caused by infection with Plasmodium spp. transmitted by Anopheles mosquitoes. The disease is endemic in tropical and subtropical regions, affecting around 45% of the global population. There is growing evidence to suggest that the host immune response influences malaria parasite transmission. Particularly, malaria can induce tolerogenic immune responses, inhibit neutrophil recruitment, and induce a shift towards Th2 immunity, protecting the host from an inflammatory response, while contributing to increased parasite transmission. We have identified mast cells (MCs) as important regulators in malaria and described multiple regulatory cytokines that rise with parasitemia, including interleukin (IL)-10. Here, we used the Cre-loxP system and non-lethal Plasmodium yoelii yoelii 17XNL to study the roles of MC-derived IL-10 in malaria immunity and transmission. Our data showed that transmission success of P. yoelii to A. stephensi was higher from female relative to male mice and from female and male mice with MCs deficient in IL-10 [MC IL-10 (-)] relative to sibling mice with normal MCs [MC IL-10 (+)]. These patterns were associated with increased plasma levels of the pro-inflammatory cytokines IL-1β and IL-6 in female MC IL-10 (-) mice and increased plasma levels of chemokines as well as the markers of neutrophil activation, myeloperoxidase, and neutrophil elastase, in male MC IL-10 (-) mice. Overall, these data confirm the role of the host immune response in malaria parasite transmission and suggest that a single MC-derived cytokine regulates parasite transmission with a female bias. Additional studies are needed to elucidate the mechanisms of these observations.