Potential role of invariant NKT cells in the control of pulmonary inflammation and CD8+ T cell response during acute influenza A virus H3N2 pneumonia

J Immunol. 2011 May 15;186(10):5590-602. doi: 10.4049/jimmunol.1002348. Epub 2011 Apr 13.

Abstract

Influenza A virus (IAV) infection results in a highly contagious respiratory illness leading to substantial morbidity and occasionally death. In this report, we assessed the in vivo physiological contribution of invariant NKT (iNKT) lymphocytes, a subset of lipid-reactive αβ T lymphocytes, on the host response and viral pathogenesis using a virulent, mouse-adapted, IAV H3N2 strain. Upon infection with a lethal dose of IAV, iNKT cells become activated in the lungs and bronchoalveolar space to become rapidly anergic to further restimulation. Relative to wild-type animals, C57BL/6 mice deficient in iNKT cells (Jα18(-/-) mice) developed a more severe bronchopneumonia and had an accelerated fatal outcome, a phenomenon reversed by the adoptive transfer of NKT cells prior to infection. The enhanced pathology in Jα18(-/-) animals was not associated with either reduced or delayed viral clearance in the lungs or with a defective local NK cell response. In marked contrast, Jα18(-/-) mice displayed a dramatically reduced IAV-specific CD8(+) T cell response in the lungs and in lung-draining mediastinal lymph nodes. We further show that this defective CD8(+) T cell response correlates with an altered accumulation and maturation of pulmonary CD103(+), but not CD11b(high), dendritic cells in the mediastinal lymph nodes. Taken together, these findings point to a role for iNKT cells in the control of pneumonia as well as in the development of the CD8(+) T cell response during the early stage of acute IAV H3N2 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, CD
  • Bronchopneumonia
  • CD11b Antigen
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Inflammation / immunology*
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / pathogenicity
  • Integrin alpha Chains
  • Lung / immunology*
  • Lung / virology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Natural Killer T-Cells / immunology*
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • Polymerase Chain Reaction
  • Viral Load

Substances

  • Antigens, CD
  • CD11b Antigen
  • Integrin alpha Chains
  • alpha E integrins