TNF Signaling Mediates Cellular Immune Function and Promotes Malaria Parasite Killing in the Mosquito

Overview

Journal bioRxiv

Date 2024 May 15

PMID 38746363

Authors

George-Rafael Samantsidis

Hyeogsun Kwon

Megan Wendland

Catherine Fonder

Ryan C Smith

Affiliations

Soon will be listed here.

Abstract

Tumor Necrosis Factor-α (TNF-α) is a proinflammatory cytokine and a master regulator of immune cell function in vertebrates. While previous studies have implicated TNF signaling in invertebrate immunity, the roles of TNF in mosquito innate immunity and vector competence have yet to be explored. Herein, we confirm the identification of a conserved TNF-α pathway in consisting of the TNF-α ligand, Eiger, and its cognate receptors Wengen and Grindelwald. Through gene expression analysis, RNAi, and injection of recombinant TNF-α, we provide direct evidence for the requirement of TNF signaling in regulating mosquito immune cell function by promoting granulocyte midgut attachment, increased granulocyte abundance, and oenocytoid rupture. Moreover, our data demonstrate that TNF signaling is an integral component of anti- immunity that limits malaria parasite survival. Together, our data support the existence of a highly conserved TNF signaling pathway in mosquitoes that mediates cellular immunity and influences infection outcomes, offering potential new approaches to interfere with malaria transmission by targeting the mosquito host.

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