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Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
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Protective role for protease-activated receptor-2 against influenza virus pathogenesis via an IFN-gamma-dependent

Khaled Khoufache1, Fanny LeBouder, Eric Morello

  • 1Unité de Virologie et Immunologie Moléculaires, Unité de Recherche 892, Institut National de la Recherche Agronomique, Domaine de Vilvert, Jouy-en-Josas, France.

Journal of Immunology (Baltimore, Md. : 1950)
|June 5, 2009
PubMed

Insights

Protease-activated receptor-2 (PAR(2)) activation protects against influenza A virus infection by boosting interferon-gamma (IFN-γ) and reducing lung inflammation. PAR(2) deficiency exacerbates influenza, highlighting its crucial protective role.

Area of Science:

  • Immunology
  • Virology
  • Respiratory Medicine

Background:

  • Protease-activated receptor-2 (PAR(2)) is expressed in the respiratory tract and modulates inflammation.
  • The role of PAR(2) in viral infections, particularly influenza, is not well understood.
  • Existing research primarily focuses on PAR(2)'s role in bacterial infections.

Purpose of the Study:

  • To investigate the role of PAR(2) in influenza A virus (IAV) pathogenesis.
  • To determine if PAR(2) activation influences IAV replication and host immune response.
  • To assess the therapeutic potential of PAR(2) agonists in influenza infection.

Main Methods:

  • In vitro studies using epithelial cells stimulated with PAR(2) agonists and infected with IAV.
  • In vivo studies using wild-type, PAR(2)-deficient, and IFN-γ-deficient mice infected with IAV.
  • Analysis of viral load, lung injury, inflammatory cell infiltration (neutrophils), and cytokine/chemokine levels (IFN-γ, RANTES) in bronchoalveolar lavage fluid.

Main Results:

  • PAR(2) stimulation inhibited IAV replication in vitro via IFN-γ production.
  • PAR(2) agonist treatment protected mice from IAV-induced lung injury and mortality.
  • Protection was associated with reduced viral load, increased IFN-γ, and decreased neutrophils and RANTES.
  • IFN-γ-deficient mice did not benefit from PAR(2) agonist treatment.
  • PAR(2)-deficient mice showed increased susceptibility to IAV, severe lung inflammation, and altered immune cell profiles.

Conclusions:

  • PAR(2) plays a significant protective role in influenza A virus infection.
  • This protection is mediated through IFN-γ production and regulation of inflammatory cell recruitment.
  • PAR(2) represents a potential therapeutic target for managing influenza infections.

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