Chapter 4 - Modulation of Mosquito Immune Defenses as a Control Strategy

Abstract

Mosquito immunity to malaria infection has received much attention since it was proposed as a major determinant of vector competence nearly 90years ago. Understanding the mosquito's immune system holds the promise of devising strategies that eliminate all parasites within the vector and thus prevent malaria transmission. Herein, we review the field of mosquito innate immunity as it pertains to malaria parasite killing, providing a historical perspective and summary of current knowledge. Mosquito immunity targets each life stage of the malaria parasite as it undergoes development within its mosquito vector. Gametes and ookinetes are killed within the midgut lumen by nitric oxide produced by the mosquito midgut. Ookinetes and developing oocysts are killed by a complex process that is initiated by ookinete migration through the midgut epithelium. This process, involving nitration and opsonization, leads to parasite killing by a mechanism that is not entirely understood. A similar process is likely responsible for the sporozoite losses that occur in the hemolymph. Mosquito immune reactions are tightly controlled by a large regulatory network of extra- and intracellular signaling cascades. Their combined action is crucial for mosquito fitness as these regulatory cascades balance the positive effects of pathogen elimination with the harmful side effects of tissue damage. Several proof of principle studies have now demonstrated that genetic manipulation of the mosquito's immune system can render susceptible mosquito species refractory to malaria parasite infection. This field is thus ready to devise a framework to evaluate these approaches in the ecological context of malaria transmission.