title: Myeloid and T Cell-Derived TNF Protects against Central Nervous System Tuberculosis.
abstract: Tuberculosis of the central nervous system (CNS-TB) is a devastating complication of tuberculosis, and tumor necrosis factor (TNF) is crucial for innate immunity and controlling the infection. TNF is produced by many cell types upon activation, in particularly the myeloid and T cells during neuroinflammation. Here we used mice with TNF ablation targeted to myeloid and T cell (MT-TNF-/-) to assess the contribution of myeloid and T cell-derived TNF in immune responses during CNS-TB. These mice exhibited impaired innate immunity and high susceptibility to cerebralMycobacterium tuberculosisinfection, a similar phenotype to complete TNF-deficient mice. Further, MT-TNF-/-mice were not able to control T cell responses and cytokine/chemokine production. Thus, our data suggested that collective TNF production by both myeloid and T cells are required to provide overall protective immunity against CNS-TB infection.
authors.affiliation: Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town , South Africa.
authors.forename: Nai-Jen
authors.initials: NJ
authors.lastname: Hsu
authors.affiliation: Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town , South Africa.
authors.forename: Ngiambudulu M
authors.initials: NM
authors.lastname: Francisco
authors.affiliation: Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town , South Africa.
authors.forename: Roanne
authors.initials: R
authors.lastname: Keeton
authors.affiliation: Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town , South Africa.
authors.forename: Nasiema
authors.initials: N
authors.lastname: Allie
authors.affiliation: CNRS UMR7355, Experimental and Molecular Immunology and Neurogenetics , Orleans , France.
authors.forename: Valérie F J
authors.initials: VF
authors.lastname: Quesniaux
authors.affiliation: CNRS UMR7355, Experimental and Molecular Immunology and Neurogenetics , Orleans , France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; South African Medical Research Council, Cape Town, South Africa; National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Muazzam
authors.initials: M
authors.lastname: Jacobs
keywords: CNS; Mycobacterium tuberculosis; T cell; myeloid; tumor necrosis factor