title: Anopheles NF-κB-regulated splicing factors direct pathogen-specific repertoires of the hypervariable pattern recognition receptor AgDscam.
abstract: Insects rely on innate immune responses controlled by the immune deficiency (IMD), Toll, and other immune signaling pathways to combat infection by a broad spectrum of pathogens. These pathways signal to downstream NF-κB family transcription factors that control specific antipathogen action via direct transcriptional control of immune effectors, hematopoiesis, and melanization. Here we show that in the Anopheles malaria vector, IMD and Toll pathways mediate species-specific defenses against Plasmodium and bacteria through the transcriptional regulation of splicing factors Caper and IRSF1 that, in turn, determine the production of pathogen-specific splice variant repertoires of the hypervariable pattern recognition receptor AgDscam. This mechanism represents an additional level of immune response regulation that may provide a previously unrecognized level of plasticity to the insect immune pathway-regulated antipathogen defenses.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205-2179, USA.
authors.forename: Yuemei
authors.initials: Y
authors.lastname: Dong
authors.forename: Chris M
authors.initials: CM
authors.lastname: Cirimotich
authors.forename: Andrew
authors.initials: A
authors.lastname: Pike
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chandra
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
mesh_terms: D000818:Animals; D000852:Anopheles / Q000276:immunology / Q000469:parasitology*; D001419:Bacteria / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D019476:Insect Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010961:Plasmodium / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D019476:Insect Proteins; D016328:NF-kappa B; D016601:RNA-Binding Proteins