Ryan C. Smith

Author summary Mosquito innate immunity is a major determinant of vector competence with significant implications in malaria transmission. During infection with the Plasmodium parasite, mosquitoes mount a sequence of immune signals originating from the mosquito midgut that stimulate the activation of mosquito immune cells (hemocytes) to limit parasite survival. Here, we provide compelling evidence that Tumor Necrosis Factor (TNF) signaling, a well-characterized immune pathway in vertebrates, is directly involved in mosquito hemocyte function and Plasmodium killing. We demonstrate that mosquito TNF signaling via the TNF ortholog, Eiger, requires the concerted function of the receptors Wengen and Grindelwald to control several aspects of mosquito immune cell biology and that ultimately limits malaria parasite survival. These data provide novel mechanistic insight into previously undescribed roles of mosquito TNF signaling in anti-Plasmodium immunity that offer potential new molecular targets for malaria control.

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