Authors
M L Simoes1; G Dimopoulos2; 1 London School of Hygiene and Tropical Medicine, UK; 2 Johns Hopkins University, United States Discussion
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 role of TEP1 has not been sufficiently addressed in the context of malaria infection with the clinically relevant human malaria parasite, Plasmodium falciparum. Using CRISPR/Cas9 genome editing, we show that the melanization of P. falciparum is independent of the TEP1-controlled complement-like system, and a small proportion of P. falciparum ookinetes are capable of evading this defense mechanism in the midgut tissue of CTL4null mosquitoes, in contrast to the complete melanization of rodent P. berghei. Furthermore, we discovered that the major anti-Plasmodium pathway Imd does not influence Plasmodium melanization. Our study proves CTL4 as one of the most potent malaria transmission-blocking targets. 
