title: Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection.
abstract: TNF is crucial for controlling Mycobacterium tuberculosis infection and understanding how will help immunomodulating the host response. Here we assessed the contribution of TNFR1 pathway from innate myeloid versus T cells. We first established the prominent role of TNFR1 in haematopoietic cells for controlling M. tuberculosis in TNFR1 KO chimera mice. Further, absence of TNFR1 specifically on myeloid cells (M-TNFR1 KO) recapitulated the uncontrolled M. tuberculosis infection seen in fully TNFR1 deficient mice, with increased bacterial burden, exacerbated lung inflammation, and rapid death. Pulmonary IL-12p40 over-expression was attributed to a prominent CD11b(+) Gr1(high) cell population in infected M-TNFR1 KO mice. By contrast, absence of TNFR1 on T-cells did not compromise the control of M. tuberculosis infection over 6-months. Thus, the protective TNF/TNFR1 pathway essential for controlling primary M. tuberculosis infection depends on innate macrophage and neutrophil myeloid cells, while TNFR1 pathway in T cells is dispensable.
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.|University of Orleans, 45000 Orleans, France.
authors.forename: Noria
authors.initials: N
authors.lastname: Segueni
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.|University of Orleans, 45000 Orleans, France.
authors.forename: Sulayman
authors.initials: S
authors.lastname: Benmerzoug
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.|University of Orleans, 45000 Orleans, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rose
authors.affiliation: University of Orleans, 45000 Orleans, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Gauthier
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.|University of Orleans, 45000 Orleans, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Bourigault
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.|University of Orleans, 45000 Orleans, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Reverchon
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.|University of Orleans, 45000 Orleans, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Philippeau
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.|University of Orleans, 45000 Orleans, France.
authors.forename: François
authors.initials: F
authors.lastname: Erard
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.|University of Orleans, 45000 Orleans, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Le Bert
authors.affiliation: Oncology-radiotherapy Department, Regional Hospital, Orleans, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bouscayrol
authors.affiliation: Oncology-radiotherapy Department, Regional Hospital, Orleans, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Wachter
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Irène
authors.initials: I
authors.lastname: Garcia
authors.affiliation: Institute for Immunology, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Kollias
authors.affiliation: Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Health Sciences Faculty, University of Cape Town, South Africa.|National Health Laboratory Service, South Africa.
authors.forename: Muazzam
authors.initials: M
authors.lastname: Jacobs
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: CNRS, UMR7355, Experimental and Molecular Immunology and Neurogenetics, 45071 Orleans, France.
authors.forename: Valerie F J
authors.initials: VF
authors.lastname: Quesniaux
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate; D008168:Lung / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000502:physiology*; D014376:Tuberculosis / Q000378:metabolism / Q000503:physiopathology
chemical_list: D016207:Cytokines; D047888:Receptors, Tumor Necrosis Factor, Type I