Enhanced protection to Mycobacterium tuberculosis infection in IL-10-deficient mice is accompanied by early and enhanced Th1 responses in the lung

Eur J Immunol. 2010 Aug;40(8):2200-10. doi: 10.1002/eji.201040433.

Abstract

IL-10 regulates the balance of an immune response between pathogen clearance and immunopathology. We show here that Mycobacterium tuberculosis (Mtb) infection in the absence of IL-10 (IL-10(-/-) mice) results in reduced bacterial loads in the lung. This reduction was preceded by an accelerated and enhanced IFN-γ response in the lung, an increased influx of CD4(+) T cells into the lung, and enhanced production of chemokines and cytokines, including CXCL10 and IL-17, in both the lung and the serum. Neutralization of IL-17 affected neither the enhanced production of CXCL10 nor the accumulation of IFN-γ-producing T cells in the lungs, but led to reduced numbers of granulocytes in the lung and reduced bacterial loads in the spleens of Mtb-infected mice. This suggests that IL-17 may contribute to dissemination of Mtb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Bacterial Load / drug effects
  • Bacterial Load / genetics
  • Bacterial Load / immunology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / microbiology
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Movement
  • Cells, Cultured
  • Chemokine CXCL10 / biosynthesis
  • Chemokine CXCL10 / genetics
  • Female
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Lung / immunology
  • Lung / metabolism*
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / pathogenicity
  • Th1-Th2 Balance / drug effects
  • Tuberculosis / genetics
  • Tuberculosis / immunology*

Substances

  • Antibodies, Blocking
  • Chemokine CXCL10
  • Interleukin-17
  • Interleukin-10
  • Interferon-gamma