title: AP-1/Fos-TGase2 axis mediates wounding-induced Plasmodium falciparum killing in Anopheles gambiae.
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.
authors.affiliation: CNRS UPR 9022, INSERM U 963, Université de Strasbourg, 15 Rue René Descartes, 67084 Strasbourg Cedex, France.
authors.forename: Sandrine E
authors.initials: SE
authors.lastname: Nsango
authors.forename: Julien
authors.initials: J
authors.lastname: Pompon
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.forename: Annika
authors.initials: A
authors.lastname: Rademacher
authors.forename: Malou
authors.initials: M
authors.lastname: Fraiture
authors.forename: Martine
authors.initials: M
authors.lastname: Thoma
authors.forename: Parfait H
authors.initials: PH
authors.lastname: Awono-Ambene
authors.forename: Roger S
authors.initials: RS
authors.lastname: Moyou
authors.forename: Isabelle
authors.initials: I
authors.lastname: Morlais
authors.forename: Elena A
authors.initials: EA
authors.lastname: Levashina
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055106:Genome-Wide Association Study; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
chemical_list: D019476:Insect Proteins; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Fos; Infectious Diseases; Insect Immunity; Malaria; Mosquito; Plasmodium; Transcription Factors; Transcription Regulation; Transcriptomics; Transglutaminases