Anopheles immune responses and vector competence are temperature-dependent

Plasmodium berghei rodent parasites are widely used as malaria infection models in the laboratory. However, we and others demonstrated that the Anopheles mosquito immune response against malaria parasite infection is parasite species-specific, and the innate immunity mechanisms involved in eliminating the clinically relevant human P. falciparum may differ from those against murine parasites. A significant difference between the two malaria species is the fact that rodent P. berghei achieves unnaturally high infection intensities in the vector mosquito, while low infection intensities for P. falciparum are usual. Using CRISPR/Cas9-mediated gene knockout and RNAi-mediated silencing of A. gambiae immune factors, we demonstrate that the immune regulation of Plasmodium is dependent on the intensity of infection. Here, we show that the differences in intensity result to some extent from the parasite’s optimal infection temperature: P. berghei sexual sporogonic development occurs at ~19 ˚C whilst P. falciparum’s is optimal at ~27 ˚C. We hypothesize that this rather large temperature difference results in a slower rate of development for the rodent parasite than for the human malaria parasite within its vector. Temperature also influences mosquito immune response kinetics and the length of exposure of the parasites to these immune responses. In this study, we predict that temperature variations and climate change may significantly affect mosquito vector competence for malaria and other pathogens, by altering the infection kinetics. Our study highlights the importance of conducting malaria laboratory-based transmission studies using clinically relevant species.