30
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available.

      The Journal of Immunology Author Choice
      Aerosols, Animals, CD4-Positive T-Lymphocytes, immunology, metabolism, Dose-Response Relationship, Immunologic, Down-Regulation, genetics, Female, GTP-Binding Proteins, biosynthesis, Genetic Predisposition to Disease, Interferon-gamma, Interleukin-12, deficiency, physiology, Interleukin-12 Subunit p35, Interleukin-17, Interleukin-23, Interleukin-23 Subunit p19, Interleukins, Lung, microbiology, pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Mycobacterium tuberculosis, growth & development, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Protein Subunits, RNA, Messenger, Tuberculosis, Pulmonary

      Read this article at

      ScienceOpenPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          IL-12p70 induced IFN-gamma is required to control Mycobacterium tuberculosis growth; however, in the absence of IL-12p70, an IL-12p40-dependent pathway mediates induction of IFN-gamma and initial bacteriostatic activity. IL-23 is an IL-12p40-dependent cytokine containing an IL-12p40 subunit covalently bound to a p19 subunit that is implicated in the induction of CD4 T cells associated with autoimmunity and inflammation. We show that in IL-23 p19-deficient mice, mycobacterial growth is controlled, and there is no diminution in either the number of IFN-gamma-producing Ag-specific CD4 T cells or local IFN-gamma mRNA expression. Conversely, there is an almost total loss of both IL-17-producing Ag-specific CD4 T cells and local production of IL-17 mRNA in these mice. The absence of IL-17 does not alter expression of the antimycobacterial genes, NO synthase 2 and LRG-47, and the absence of IL-23 or IL-17, both of which are implicated in mediating inflammation, fails to substantially affect the granulomatous response to M. tuberculosis infection of the lung. Despite this redundancy, IL-23 is required to provide a moderate level of protection in the absence of IL-12p70, and this protection correlates with a requirement for IL-23 in the IL-12p70-independent induction of Ag-specific, IFN-gamma-producing CD4 T cells. We also show that IL-23 is required for the induction of an IL-17-producing Ag-specific phenotype in naive CD4 T cells in vitro and that absence of IL-12p70 promotes an increase in the number of IL-17-producing Ag-specific CD4 T cells both in vitro and in vivo.

          Related collections

          Author and article information

          Comments

          Comment on this article