Pathways:
IFN-gamma pathway
Host Molecules Involved:
Protease-activated receptor-2 (PAR(2)), associated with inflammation at mucosal surfaces.
Tissues:
Respiratory tract, mucosal surfaces, bronchoalveolar lavages
Systems:
Lungs, immune system
Interactions:
PAR(2) enhances IFN- gamma production.
Mechanisms:
- In vitro, PAR(2) inhibits influenza virus type A (IAV) replication through the production of IFN-gamma.
- In vivo, PAR(2) protects mice from IAV-induced acute lung injury and death.
- This effect is associated with an enhanced clearance of IAV in the lungs, enhanced IFN- gamma production, a reduced number of neutrophils and RANTES release in bronchoalveolar fluids.
- PAR(2)-deficient mice were more susceptible to influenza infection, with more severe lung inflammation, increased neutrophil counts and RANTES concentration, and reduced IFN- gamma levels.
Effects:
During IAV infection, PAR(2) protects the host through increased IFN-gamma production and reduced excessive accumulation of inflammatory cells to lung alveoli.
Reference:
Khoufache, K., LeBouder, F., et al. (2009) Protective role for protease-activated receptor-2 against influenza virus pathogenesis via an IFN-gamma-dependent pathway. J Immunol 182, 7795-7802.
