MAPK ERK Signaling Regulates the TGF-β1-Dependent Mosquito Response to Plasmodium falciparum

PLoS Pathogens

Kong Wai Cheung¹  Shirley Luckhart¹  Win Surachetpong¹  Naresh Singh¹ 

[1] Department of Medical Microbiology and Immunology, University of California at Davis, Davis, California, United States of America

关键词: Parasitic diseases;    Malarial parasites;    MAPK signaling cascades;    Plasmodium;    Mosquitoes;    Gene expression;    ERK signaling cascade;    Malaria;   

DOI  :  10.1371/journal.ppat.1000366

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Malaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these responses during parasite development. Here we demonstrate that the MEK-ERK signaling pathway in Anopheles is controlled by ingested human TGF-β1 and finely tunes mosquito innate immunity to parasite infection. Specifically, MEK-ERK signaling was dose-dependently induced in response to TGF-β1 in immortalized cells in vitro and in the A. stephensi midgut epithelium in vivo. At the highest treatment dose of TGF-β1, inhibition of ERK phosphorylation increased TGF-β1-induced expression of the anti-parasite effector gene nitric oxide synthase (NOS), suggesting that increasing levels of ERK activation negatively feed back on induced NOS expression. At infection levels similar to those found in nature, inhibition of ERK activation reduced P. falciparum oocyst loads and infection prevalence in A. stephensi and enhanced TGF-β1-mediated control of P. falciparum development. Taken together, our data demonstrate that malaria parasite development in the mosquito is regulated by a conserved MAPK signaling pathway that mediates the effects of an ingested cytokine.

【 授权许可】

CC BY