AP-1/Fos-TGase2 axis mediates wounding-induced Plasmodium falciparum killing in Anopheles gambiae

J Biol Chem. 2013 May 31;288(22):16145-54. doi: 10.1074/jbc.M112.443267. Epub 2013 Apr 16.

Abstract

Anopheline mosquitoes are the only vectors of human malaria worldwide. It is now widely accepted that mosquito immune responses play a crucial role in restricting Plasmodium development within the vector; therefore, further dissection of the molecular mechanisms underlying these processes should inform new vector control strategies urgently needed to roll back the disease. Here, using genome-wide transcriptional profiling, bioinformatics, and functional gene analysis, we identify a new axis of mosquito resistance to monoclonal Plasmodium falciparum infections that includes the AP-1 transcription factor Fos and the transglutaminase 2 (TGase2), a cross-linking enzyme with known roles in wound responses. We demonstrate that Fos regulates induction of TGase2 expression after wounding but does not affect expression of the components of the well characterized complement-like system. Silencing of Fos or of TGase2 aborts the wounding-induced mosquito killing of P. falciparum. These results reveal multiple signaling pathways that are required for efficient Plasmodium killing in Anopheles gambiae.

Keywords: Fos; Infectious Diseases; Insect Immunity; Malaria; Mosquito; Plasmodium; Transcription Factors; Transcription Regulation; Transcriptomics; Transglutaminases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / genetics
  • Anopheles / metabolism*
  • Anopheles / parasitology*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Genome-Wide Association Study
  • Humans
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Plasmodium falciparum / metabolism*
  • Protein Glutamine gamma Glutamyltransferase 2
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism*
  • Transglutaminases / genetics
  • Transglutaminases / metabolism*

Substances

  • Insect Proteins
  • Proto-Oncogene Proteins c-fos
  • Transcription Factor AP-1
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins