IL-23 and IL-17 in the Establishment of Protective Pulmonary CD4+ T Cell Responses After Vaccination and During Mycobacterium Tuberculosis Challenge

Nat Immunol. 2007 Apr;8(4):369-77. doi: 10.1038/ni1449. Epub 2007 Mar 11.

Abstract

Interferon-gamma is key in limiting Mycobacterium tuberculosis infection. Here we show that vaccination triggered an accelerated interferon-gamma response by CD4(+) T cells in the lung during subsequent M. tuberculosis infection. Interleukin 23 (IL-23) was essential for the accelerated response, for early cessation of bacterial growth and for establishment of an IL-17-producing CD4(+) T cell population in the lung. The recall response of the IL-17-producing CD4(+) T cell population occurred concurrently with expression of the chemokines CXCL9, CXCL10 and CXCL11. Depletion of IL-17 during challenge reduced the chemokine expression and accumulation of CD4(+) T cells producing interferon-gamma in the lung. We propose that vaccination induces IL-17-producing CD4(+) T cells that populate the lung and, after challenge, trigger the production of chemokines that recruit CD4(+) T cells producing interferon-gamma, which ultimately restrict bacterial growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Immunohistochemistry
  • Interleukin-17 / immunology*
  • Interleukin-23 / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Interleukin-17
  • Interleukin-23
  • Tuberculosis Vaccines