CISH controls bacterial burden early after infection with Mycobacterium tuberculosis in mice

Tuberculosis (Edinb). 2017 Dec;107:175-180. doi: 10.1016/j.tube.2017.09.007. Epub 2017 Sep 22.

Abstract

CISH gene has been associated with increased susceptibility to human tuberculosis. We found that cish-/- mice had higher M. tuberculosis load in spleens and lungs up to 2.5 weeks after infection but not later compared to controls. Cish mRNA levels were increased in lungs at early and late time points after M. tuberculosis infection. In relation, the titers of inos and tnf mRNA in lungs were reduced early after infection of cish-/- mice. The transfer of cish-/- and control T cells conferred rag1-/- mice similar protection to infection with M. tuberculosis. Macrophages showed increased cish mRNA levels after M. tuberculosis infection in vitro. However, mycobacterial uptake and growth in cish-/- and control macrophages was similar. Thus, we here show that CISH mediates control of M. tuberculosis in mice early after infection via regulation of innate immune mechanisms.

Keywords: Cytokine-inducible SRC homology 2 domain gene; Cytokines; Macrophage; Mycobacterium tuberculosis; SOCS; T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Host-Pathogen Interactions
  • Immunity, Innate
  • Lung / immunology
  • Lung / metabolism*
  • Lung / microbiology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycobacterium tuberculosis / growth & development*
  • Mycobacterium tuberculosis / immunology
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Phenotype
  • Suppressor of Cytokine Signaling Proteins / deficiency
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Time Factors
  • Tuberculosis, Pulmonary / genetics
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / metabolism*
  • Tuberculosis, Pulmonary / microbiology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Suppressor of Cytokine Signaling Proteins
  • Tumor Necrosis Factor-alpha
  • cytokine inducible SH2-containing protein
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse