Protective role of LGP2 in influenza virus pathogenesis.
Influenza A virus triggers a contagious respiratory disease that can cause considerable morbidity and mortality. Using an in vitro approach, we previously demonstrated that the pattern recognition receptor retinoic acid-inducible gene I (RIG-I) plays a key role in influenza A virus-mediated immune response. However, the importance of RIG-I signaling in vivo has not been thoroughly examined, because of the lack of an appropriate mouse models. To circumvent this issue, we generated a new transgenic mouse overexpressing LGP2 (hereafter, "LGP2 TG mice"), a major regulator of the RIG-I signaling pathway. The time course of several parameters was compared in infected wild-type and LGP2 TG mice. We found that LGP2 TG mice displayed significantly reduced inflammatory mediators and a lower leukocyte infiltration into the bronchoalveolar airspace. More importantly, LGP2 TG mice had a significant survival advantage. Hence, our in vivo study reveals that LGP2 is a major downregulator of the influenza A virus-triggered detrimental inflammatory response.
Institut Pasteur, Unité de Défense Innée et Inflammation Inserm, U874.
Mustapha
M
Si-Tahar
Institut Pasteur, Unité de Défense Innée et Inflammation Inserm, U874.
Fany
F
Blanc
Institut Pasteur, Unité de Défense Innée et Inflammation Inserm, U874.
Laetitia
L
Furio
Institut Pasteur, Unité de Neuroimmunologie Virale CNRS UMR3569.
Damien
D
Chopy
Institut Pasteur, Unité de Défense Innée et Inflammation Inserm, U874.
Viviane
V
Balloy
Institut Pasteur, Unité de Neuroimmunologie Virale CNRS UMR3569.
Monique
M
Lafon
Institut Pasteur, Unité de Défense Innée et Inflammation Inserm, U874.
Michel
M
Chignard
Institut Pasteur, Unité d'Histotechnologie et Pathologie.
Laurence
L
Fiette
Institut Pasteur, Plate-Forme Technologique Centre d'Ingenierie Genetique Murine.
Francina
F
Langa
Laboratoire de Virologie moléculaire et vectorologie, Institut Pasteur, Paris, France.
Pierre
P
Charneau
Institut Pasteur, Unité de Défense Innée et Inflammation Inserm, U874.
Julien
J
Pothlichet
D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D018836:Inflammation Mediators / Q000032:analysis; D009980:Influenza A virus / Q000502:physiology*; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology; D020365:RNA Helicases / Q000378:metabolism*; D015398:Signal Transduction; D016019:Survival Analysis
D018836:Inflammation Mediators; C547666:Dhx58 protein, mouse; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases
immunity; inflammation; lung; signal transduction; viral