Immune Regulation of Plasmodium Is Anopheles Species Specific and Infection Intensity Dependent.

Maria L Simões,Abhai Tripathi,Godfree Mlambo,Yuemei Dong,George Dimopoulos,Bruno Lemaitre

doi:10.1128/mbio.01631-17

Abstract

ABSTRACTMalaria parasite ookinetes must traverse the vector mosquito midgut epithelium to transform into sporozoite-producing oocysts. The Anopheles innate immune system is a key regulator of this process, thereby determining vector competence and disease transmission. The role of Anopheles innate immunity factors as agonists or antagonists of malaria parasite infection has been previously determined using specific single Anopheles-Plasmodium species combinations. Here we show that the two C-type lectins CTL4 and CTLMA2 exert differential agonistic and antagonistic regulation of parasite killing in African and South American Anopheles species. The C-type lectins regulate both parasite melanization and lysis through independent mechanisms, and their implication in parasite melanization is dependent on infection intensity rather than mosquito-parasite species combination. We show that the leucine-rich repeat protein LRIM1 acts as an antagonist on the development of Plasmodium ookinetes and as a regulator of oocyst size and sporozoite production in the South American mosquito Anopheles albimanus. Our findings explain the rare observation of human Plasmodium falciparum melanization and define a key factor mediating the poor vector competence of Anopheles albimanus for Plasmodium berghei and Plasmodium falciparum.

Highlights

Malaria parasite ookinetes must traverse the vector mosquito midgut epithelium to transform into sporozoite-producing oocysts
RNA interference (RNAi)-mediated silencing of A. gambiae C-type lectins CTL4 (AgCTL4) and AgCTLMA2 resulted in a reduced intensity of infection with P. berghei, and melanization was observed in 63% of AgCTL4-silenced and 26% of AgCTLMA2-silenced mosquitoes (Fig. 1A)
The study by Osta et al [12] showing that depletion of CTL4 and CTLMA2 in the A. gambiae G3 strain results in melanotic encapsulation of P. berghei PbCTRPp.GFP ookinetes has established that gene system as a parasite melanization model

Summary

Introduction

Malaria parasite ookinetes must traverse the vector mosquito midgut epithelium to transform into sporozoite-producing oocysts. The role of Anopheles innate immunity factors as agonists or antagonists of malaria parasite infection has been previously determined using specific single Anopheles-Plasmodium species combinations. We show that the functions of CTL4 and CTLMA2 have diverged in different vector species and can be both agonistic and antagonistic for Plasmodium infection Their protection against parasite melanization in Anopheles gambiae is dependent on infection intensity, rather than the mosquito-parasite combination. Transmission of the malaria protozoan parasite Plasmodium to the vertebrate host involves a complex infection cycle in the mosquito vector that includes sexual sporogonic development through several stages As it feeds upon blood, the female mosquito ingests Plasmodium gametocytes that mature into gametes within the midgut lumen; fertilization of these gametes produces zygotes, which in turn develop into motile ookinetes. We have previously shown that the A. gambiae molecular responses to infection with either P. berghei or P. falciparum parasites differ greatly at the level of gene transcript abundance, as well as with regard to immune gene function [8, 9]

Methods

Results

Conclusion