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© Research
Publication : Journal of immunology (Baltimore, Md. : 1950)

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of immunology (Baltimore, Md. : 1950) - 15 May 2011

Paget C, Ivanov S, Fontaine J, Blanc F, Pichavant M, Renneson J, Bialecki E, Pothlichet J, Vendeville C, Barba-Spaeth G, Huerre MR, Faveeuw C, Si-Tahar M, Trottein F,

Link to Pubmed [PMID] – 21490153

Link to DOI – 10.4049/jimmunol.1002348

J Immunol 2011 May; 186(10): 5590-602

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.