Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages

J Biol Chem. 2012 Mar 16;287(12):8816-29. doi: 10.1074/jbc.M111.304758. Epub 2012 Jan 31.

Abstract

Invariant natural killer T (iNKT) cells are non-conventional lipid-reactive αβ T lymphocytes that play a key role in host responses during viral infections, in particular through the swift production of cytokines. Their beneficial role during experimental influenza A virus (IAV) infection has recently been proposed, although the mechanisms involved remain elusive. Here we show that during in vivo IAV infection, mouse pulmonary iNKT cells produce IFN-γ and IL-22, a Th17-related cytokine critical in mucosal immunity. Although permissive to viral replication, IL-22 production by iNKT cells is not due to IAV infection per se of these cells but is indirectly mediated by IAV-infected dendritic cells (DCs). We show that activation of the viral RNA sensors TLR7 and RIG-I in DCs is important for triggering IL-22 secretion by iNKT cells, whereas the NOD-like receptors NOD2 and NLRP3 are dispensable. Invariant NKT cells respond to IL-1β and IL-23 provided by infected DCs independently of the CD1d molecule to release IL-22. In vitro, IL-22 protects IAV-infected airway epithelial cells against mortality but has no role on viral replication. Finally, during early IAV infection, IL-22 plays a positive role in the control of lung epithelial damages. Overall, IAV infection of DCs activates iNKT cells, providing a rapid source of IL-22 that might be beneficial to preserve the lung epithelium integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Epithelial Cells / cytology*
  • Epithelial Cells / immunology
  • Humans
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / physiology*
  • Influenza, Human / immunology*
  • Influenza, Human / physiopathology*
  • Influenza, Human / virology
  • Interleukin-22
  • Interleukins / immunology*
  • Lung / cytology*
  • Lung / immunology
  • Lung / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Natural Killer T-Cells / immunology*

Substances

  • Interleukins