Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection.

• DOI: 10.1038/srep22454
• Publication Date: 2016-03-02T11:16:52Z
• Authors: Noria Segueni; Sulayman Benmerzoug; Stéphanie Rose; Amandine Gauthier; Marie-Laure Bouri...; Flora Reverchon; Amandine Philippeau; François Erard; Marc Le Bert; Hélène Bouscayrol; Thierry Wachter; Irène Garcia; George Kollias; Muazzam Jacobs; Bernhard Ryffel; Valerie F.J. Ques...
• Keywords: Mice, Knockout; [SDV.IMM] Life Sciences [q-bio]/Immunology; info:eu-repo/classification/ddc/616.07; Bone Marrow Cells; Mycobacterium tuberculosis; ddc:616.07; [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity; Article; Immunity, Innate; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Receptors, Tumor Necrosis Factor, Type I; Animals; Cytokines; Tuberculosis; [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity; Lung

Abstract TNF is crucial for controlling Mycobacterium tuberculosis infection and understanding how will help immunomodulating the host response. Here we assessed contribution of TNFR1 pathway from innate myeloid versus T cells. We first established prominent role in haematopoietic cells M. KO chimera mice. Further, absence specifically on (M-TNFR1 KO) recapitulated uncontrolled seen fully deficient mice, with increased bacterial burden, exacerbated lung inflammation, rapid death. Pulmonary IL-12p40 over-expression was attributed to a CD11b + Gr1 high cell population infected M-TNFR1 By contrast, T-cells did not compromise control over 6-months. Thus, protective TNF/TNFR1 essential primary depends macrophage neutrophil cells, while dispensable.