Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection.
J Leukoc Biol
; 91(3): 357-68, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22003207
ABSTRACT
Little is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6C(hi)Ly6G(-) inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (Jα18(-/-) mice) have increased levels of inflammatory monocytes, which correlated with increased lung injury and mortality (but not viral load). Activation of iNKT cells correlated with reduction of MCP-1 levels and improved outcome. iNKT cells were able to selectively lyse infected, MCP-1-producing monocytes in vitro, in a CD1d-dependent process. Our study provides a detailed profile and kinetics of innate immune cells in the lungs during severe IAV infection, highlighting inflammatory monocytes as the major infiltrate and identifying a role for iNKT cells in control of these cells and lung immune-pathology.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
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Monócitos
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Infecções por Orthomyxoviridae
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Células T Matadoras Naturais
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Inflamação
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Pulmão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido