MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum.

Win Surachetpong, Naresh Singh, Kong Wai Cheung, Shirley Luckhart

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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-beta1 and finely tunes mosquito innate immunity to parasite infection. Specifically, MEK-ERK signaling was dose-dependently induced in response to TGF-beta1 in immortalized cells in vitro and in the A. stephensi midgut epithelium in vivo. At the highest treatment dose of TGF-beta1, inhibition of ERK phosphorylation increased TGF-beta1-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-beta1-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.

Original languageEnglish (US)
JournalPLoS Pathogens
Volume5
Issue number4
DOIs
StatePublished - Apr 2009

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Transforming Growth Factor beta1
Plasmodium falciparum
Culicidae
Parasites
Anopheles
Nitric Oxide Synthase
Malaria
Infection
Parasitic Diseases
Plasmodium
Oocysts
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Innate Immunity
Genes
Epithelium
Phosphorylation
Cytokines

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum. / Surachetpong, Win; Singh, Naresh; Cheung, Kong Wai; Luckhart, Shirley.

In: PLoS Pathogens, Vol. 5, No. 4, 04.2009.

Research output: Contribution to journalArticle

Surachetpong, Win ; Singh, Naresh ; Cheung, Kong Wai ; Luckhart, Shirley. / MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum. In: PLoS Pathogens. 2009 ; Vol. 5, No. 4.
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