Hemocyte differentiation to the megacyte lineage enhances mosquito immunity against Plasmodium

Abstract

Activation of <i>Toll</i> signaling in <i>Anopheles gambiae</i> by silencing <i>Cactus</i>, a suppressor of this pathway, enhances local release of hemocyte-derived microvesicles (HdMv), promoting activation of the mosquito complement-like system, which eliminates <i>Plasmodium</i> ookinetes. We uncovered the mechanism of this immune enhancement. <i>Cactus</i> silencing triggers a <i>Rel1</i>-mediated differentiation of granulocytes to the megacyte lineage, a new subpopulation of giant cells, resulting in a dramatic increase in the proportion of circulating megacytes. Megacytes are very plastic cells that are massively recruited to the basal midgut surface in response to <i>Plasmodium</i> infection. We show that <i>Toll</i> signaling modulates hemocyte differentiation and that megacyte recruitment to the midgut greatly enhances mosquito immunity against <i>Plasmodium</i>.