tetano
Editor, Senior Moderator
First Published on January 31, 2012, doi: 10.1074/jbc.M111.304758 jbc.M111.304758.
Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damage
Christophe Paget1,
Stoyan Ivanov1,
Josette Fontaine1,
Joelle Renneson1,
Fany Blanc2,
Muriel Pichavant1,
Laure Dumoutier3,
Bernhard Ryffel4,
Jean Christophe Renauld3,
Philippe Gosset5,
Pierre Gosset6,
Mustapha Si-Tahar2,
Christelle Faveeuw5 and
Fran?ois Trottein1,*
+ Author Affiliations
1 Institut Pasteur Lille, France;
2 Institut Pasteur Paris, France;
3 Ludwig Institute, Belgium;
4 CNRS, France;
5 Institut Pasteur lille, France;
6 Hopital Saint Vincent, France
↵* Corresponding author; email: francois.trottein@pasteur-lille.fr
Capsule
Background: Invariant natural killer T (iNKT) cells play a beneficial role during influenza A virus (IAV) infection
Results: iNKT cells produce IL-22 during infection and IL-22 prevents the IAV-triggered cell death of pulmonary epithelium
Conclusion: IL-22 produced by iNKT cells might be important during IAV infection
Significance: Understanding how iNKT cells function during IAV infection might be instrumental to control IAV-associated pathogenesis
Abstract
Invariant natural killer T (iNKT) cells are non-conventional lipid-reactive ab 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-g 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 whilst the NOD-like receptors NOD2 and NLRP3 are dispensable. Invariant NKT cells respond to IL-1b 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.
http://www.jbc.org/content/early/2012/01/31/jbc.M111.304758.abstract
Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damage
Christophe Paget1,
Stoyan Ivanov1,
Josette Fontaine1,
Joelle Renneson1,
Fany Blanc2,
Muriel Pichavant1,
Laure Dumoutier3,
Bernhard Ryffel4,
Jean Christophe Renauld3,
Philippe Gosset5,
Pierre Gosset6,
Mustapha Si-Tahar2,
Christelle Faveeuw5 and
Fran?ois Trottein1,*
+ Author Affiliations
1 Institut Pasteur Lille, France;
2 Institut Pasteur Paris, France;
3 Ludwig Institute, Belgium;
4 CNRS, France;
5 Institut Pasteur lille, France;
6 Hopital Saint Vincent, France
↵* Corresponding author; email: francois.trottein@pasteur-lille.fr
Capsule
Background: Invariant natural killer T (iNKT) cells play a beneficial role during influenza A virus (IAV) infection
Results: iNKT cells produce IL-22 during infection and IL-22 prevents the IAV-triggered cell death of pulmonary epithelium
Conclusion: IL-22 produced by iNKT cells might be important during IAV infection
Significance: Understanding how iNKT cells function during IAV infection might be instrumental to control IAV-associated pathogenesis
Abstract
Invariant natural killer T (iNKT) cells are non-conventional lipid-reactive ab 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-g 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 whilst the NOD-like receptors NOD2 and NLRP3 are dispensable. Invariant NKT cells respond to IL-1b 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.
http://www.jbc.org/content/early/2012/01/31/jbc.M111.304758.abstract