title: Regulation of anti-Plasmodium immunity by a LITAF-like transcription factor in the malaria vector Anopheles gambiae.
abstract: The mosquito is the obligate vector for malaria transmission. To complete its development within the mosquito, the malaria parasite Plasmodium must overcome the protective action of the mosquito innate immune system. Here we report on the involvement of the Anopheles gambiae orthologue of a conserved component of the vertebrate immune system, LPS-induced TNFα transcription factor (LITAF), and its role in mosquito anti-Plasmodium immunity. An. gambiae LITAF-like 3 (LL3) expression is up-regulated in response to midgut invasion by both rodent and human malaria parasites. Silencing of LL3 expression greatly increases parasite survival, indicating that LL3 is part of an anti-Plasmodium defense mechanism. Electrophoretic mobility shift assays identified specific LL3 DNA-binding motifs within the promoter of SRPN6, a gene that also mediates mosquito defense against Plasmodium. Further experiments indicated that these motifs play a direct role in LL3 regulation of SRPN6 expression. We conclude that LL3 is a transcription factor capable of modulating SRPN6 expression as part of the mosquito anti-Plasmodium immune response.
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Smith
authors.forename: Abraham G
authors.initials: AG
authors.lastname: Eappen
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Radtke
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007303:Insect Vectors / Q000276:immunology* / Q000469:parasitology; D008288:Malaria / Q000635:transmission; D010961:Plasmodium / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D019476:Insect Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors