title: Potential role of invariant NKT cells in the control of pulmonary inflammation and CD8+ T cell response during acute influenza A virus H3N2 pneumonia.
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.
authors.affiliation: Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59019 Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Paget
authors.forename: Stoyan
authors.initials: S
authors.lastname: Ivanov
authors.forename: Josette
authors.initials: J
authors.lastname: Fontaine
authors.forename: Fany
authors.initials: F
authors.lastname: Blanc
authors.forename: Muriel
authors.initials: M
authors.lastname: Pichavant
authors.forename: Joelle
authors.initials: J
authors.lastname: Renneson
authors.forename: Emilie
authors.initials: E
authors.lastname: Bialecki
authors.forename: Julien
authors.initials: J
authors.lastname: Pothlichet
authors.forename: Catherine
authors.initials: C
authors.lastname: Vendeville
authors.forename: Giovanna
authors.initials: G
authors.lastname: Barba-Spaeth
authors.forename: Giovanna
authors.initials: G
authors.lastname: Barba-Speath
authors.forename: Michel-René
authors.initials: MR
authors.lastname: Huerre
authors.forename: Christelle
authors.initials: C
authors.lastname: Faveeuw
authors.forename: Mustapha
authors.initials: M
authors.lastname: Si-Tahar
authors.forename: François
authors.initials: F
authors.lastname: Trottein
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD; D001996:Bronchopneumonia; D039481:CD11b Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000472:pathogenicity; D039001:Integrin alpha Chains; D008168:Lung / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D011024:Pneumonia, Viral / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; C091367:alpha E integrins