CTL4 melanization-based regulation of human malaria infection

Tuesday, November 15, 2022

1:54 PM – 2:06 PM PT

Location: Vancouver Convention Centre, Meeting Room 220

Presenting Author(s)

Maria Luisa Simoes

Assistant Professor
London School of Hygiene and Tropical Medicine
London, England, United Kingdom

Co-Author(s)

YD

Yuemei Dong

Johns Hopkins University
Baltimore, Maryland
GM

Godfree Mlambo

Johns Hopkins University
Baltimore, Maryland
George Dimopoulos

Professor
Johns Hopkins University
Baltimore, Maryland

Melanization is one of the most effective innate defense mechanisms in mosquito vectors. Numerous studies have shown that the Anopheles TEP1-controlled complement-like system is essential for melanization of the rodent model malaria parasite Plasmodium berghei, which evades this defense by recruiting C-type lectins. But the roles of CTL4 and TEP1 have not been sufficiently addressed in the context of malaria infection with the clinically relevant human malaria parasite, Plasmodium falciparum. Using CRISPR/Cas9-based C-type lectin 4 knockout, we show that A. gambiae can mount melanization-based refractoriness to the human malaria parasite in a TEP1-independent manner, and a small proportion of P. falciparum ookinetes are capable of evading this defense mechanism in the midgut tissue of CTL4^null mosquitoes, in contrast to the complete melanization of rodent P. berghei. Our study proves CTL4 as an essential host factor for P. falciparum transmission and one of the most potent mosquito-encoded malaria transmission-blocking targets, and highlights discrepancies in the Anopheles innate immunity response to P. falciparum versus P. berghei, while stressing the importance of conducting malaria laboratory-based transmission studies using clinically relevant parasites.