Mosquito immune responses and compatibility between Plasmodium parasites and anopheline mosquitoes

Four new An. gambiae (G3) genes were identified that, when silenced, have a different effect on P. berghei (Anka 2.34) and P. falciparum (3D7) infections. Orthologs of these genes, as well as LRIM1 and CTL4, were also silenced in An. stephensi (Nijmegen Sda500) females infected with P. yoelii (17XNL). For five of the six genes tested, silencing had the same effect on infection in the P. falciparum-An. gambiae and P. yoelii-An. stephensi parasite-vector combinations. Although silencing LRIM1 or CTL4 has no effect in An. stephensi females infected with P. yoelii, when An. gambiae is infected with the same parasite, silencing these genes has a dramatic effect. In An. gambiae (G3), TEP1, LRIM1 or LRIM2 silencing reverts lysis and melanization of P. yoelii, while CTL4 silencing enhances melanization.There is a broad spectrum of compatibility, the extent to which the mosquito immune system limits infection, between different Plasmodium strains and particular mosquito strains that is mediated by TEP1/LRIM1 activation. The interactions between highly compatible animal models of malaria, such as P. yoelii (17XNL)-An. stephensi (Nijmegen Sda500), is more similar to that of P. falciparum (3D7)-An. gambiae (G3).Mosquitoes transmit many infectious diseases, including malaria, lymphatic filariasis, yellow fever, and dengue. Among these diseases, malaria is by far the most costly in terms of human health. It is endemic to more than 100 countries and causes 550 million cases per year, with the highest mortality in children from sub-Saharan Africa. Malaria transmission to humans requires a competent mosquito species, as Plasmodium parasites must undergo a complex developmental cycle and survive the defense responses of their insect host. In Africa, Anopheles gambiae is the major vector of Plasmodium falciparum infection, which causes the most aggressive form of human malaria.The Plasmodium berghei (murine malaria) model is one of the most widely used experimental systems to study ma