title: Type I interferon licenses enhanced innate recognition and transcriptional responses to Franciscella tularensis live vaccine strain.
abstract: The innate inflammatory response to Francisella tularensis (Ft) in macrophages is significantly governed by the expression of type I interferon (IFN). Previously, the proteolytic processing and maturation of pro-IL-1β protein was shown to depend upon type I IFN expression. We show in this report that paracrine type I IFN can profoundly enhance innate recognition and TLR-dependent transcriptional responses to Ft infection upstream of its role in inflammasome regulation in both primary human monocyte-derived macrophages and primary murine peritoneal macrophages but not murine bone marrow-derived macrophages. This type I IFN-enhanced response is synergistic with TLR2 transcriptional responses, partially TLR2-independent, but strictly MyD88-dependent.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland, Baltimore (UMB), School of Medicine, Baltimore, MD, USA.
authors.forename: Katharina
authors.initials: K
authors.lastname: Richard
authors.affiliation: Department of Microbiology and Immunology, University of Maryland, Baltimore (UMB), School of Medicine, Baltimore, MD, USA svogel@som.umaryland.edu.
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Vogel
authors.affiliation: Department of Microbiology and Immunology, University of Maryland, Baltimore (UMB), School of Medicine, Baltimore, MD, USA.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Perkins
mesh_terms: D000818:Animals; D005604:Francisella tularensis / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009928:Organ Specificity; D000067996:RAW 264.7 Cells; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014158:Transcription, Genetic; D014406:Tularemia
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016899:Interferon-beta
keywords: Francisella tularensis LVS; IFN-β; TLR2; macrophage; type I interferon