Mosquito innate immunity


Malaria parasite killing in the mosquito host

With more than 200 million cases and over 400,000 deaths, malaria is the deadliest of all mosquito-borne diseases. Transmitted by mosquitoes of the genus Anopheles, much of our work has focused on understanding the mechanisms that influence parasite survival in the mosquito host. Blood meal-derived blood components and the mosquito microbiota have been shown to limit parasite viability in the midgut lumen, while the mosquito innate immune response has been shown to act as an integral factor in determining both ookinete and oocyst survival (Smith et al, 2014).

While it is well-known that mosquito immunity influences malaria parasite survival, our mechanistic understanding of how malaria parasites are killed in the mosquito host remains incomplete. To better understand these anti-Plasmodium immune responses, our work has led to the characterization of a LITAF-like transcription factor, LL3, in the mosquito innate immune response, and demonstrated its role as a major antagonist of malaria parasite development (Smith et al., 2012). Regulating the differentiation of mosquito immune cells known as hemocytes, this work has reshaped our understanding of parasite killing in the mosquito host by defining parasite killing into “early” and “late-phase” immune responses acting on different stages of malaria parasites (Smith et al., 2015; Smith et al., 2016).

New evidence suggests that these multimodal immune responses are independent (Kwon et al., 2017), supporting that the immune mechanisms that determine ookinete and oocyst survival are distinct. Recent data also suggests that there is heterogeneity in the mechanisms that determine oocyst survival, with strain-specific differences shaped by genetic background limit oocyst survival, demonstrating the importance of genetics in shaping mosquito vector competence (Kwon et al., 2017).

Current experiments are aimed at further exploring these multimodal mechanisms of parasite killing.