title: STAT3 Represses Nitric Oxide Synthesis in Human Macrophages upon Mycobacterium tuberculosis Infection.
abstract: Mycobacterium tuberculosis is a successful intracellular pathogen. Numerous host innate immune responses signaling pathways are induced upon mycobacterium invasion, however their impact on M. tuberculosis replication is not fully understood. Here we reinvestigate the role of STAT3 specifically inside human macrophages shortly after M. tuberculosis uptake. We first show that STAT3 activation is mediated by IL-10 and occurs in M. tuberculosis infected cells as well as in bystander non-colonized cells. STAT3 activation results in the inhibition of IL-6, TNF-α, IFN-γ and MIP-1β. We further demonstrate that STAT3 represses iNOS expression and NO synthesis. Accordingly, the inhibition of STAT3 is detrimental for M. tuberculosis intracellular replication. Our study thus points out STAT3 as a key host factor for M. tuberculosis intracellular establishment in the early stages of macrophage infection.
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: Queval
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Ok-Ryul
authors.initials: OR
authors.lastname: Song
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Deboosère
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Delorme
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Debrie
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Iantomasi
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Veyron-Churlet
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Jouny
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Keely
authors.initials: K
authors.lastname: Redhage
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Gaspard
authors.initials: G
authors.lastname: Deloison
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Baulard
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Mathias
authors.initials: M
authors.lastname: Chamaillard
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.affiliation: University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
authors.forename: Priscille
authors.initials: P
authors.lastname: Brodin
mesh_terms: D000818:Animals; D002460:Cell Line; D054407:Chemokine CCL4 / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000067996:RAW 264.7 Cells; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054407:Chemokine CCL4; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II