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

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.

• Authors: Christophe Paget, Stoyan Ivanov, Josette Fontaine, Joelle Renneson, Fany Blanc, Muriel Pichavant, Laure Dumoutier, Bernhard Ryffel, Jean Christophe Renauld, Philippe Gosset, Pierre Gosset, Mustapha Si-Tahar, Christelle Faveeuw, François Trottein
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 12 Pg. 8816-29 (Mar 16 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 22294696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukins
• interleukin-22

Topics

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