| First Author | Califano D | Year | 2018 |
| Journal | Mucosal Immunol | Volume | 11 |
| Issue | 1 | Pages | 209-219 |
| PubMed ID | 28513592 | Mgi Jnum | J:319446 |
| Mgi Id | MGI:6863445 | Doi | 10.1038/mi.2017.41 |
| Citation | Califano D, et al. (2018) IFN-gamma increases susceptibility to influenza A infection through suppression of group II innate lymphoid cells. Mucosal Immunol 11(1):209-219 |
| abstractText | Increased levels of interferon-gamma (IFN-gamma) are routinely observed in the respiratory tract following influenza virus infection, yet its potential role remains unclear. We now demonstrate that influenza-induced IFN-gamma restricts protective innate lymphoid cell group II (ILC2) function in the lung following challenge with the pandemic H1N1 A/CA/04/2009 (CA04) influenza virus. Specifically, IFN-gamma deficiency resulted in enhanced ILC2 activity, characterized by increased production of interleukin (IL)-5 and amphiregulin, and improved tissue integrity, yet no change in ILC2 numbers, viral load or clearance. We further found that IFN-gamma-deficient mice, as well as wild-type animals treated with neutralizing anti-IFN-gamma antibody, exhibited decreased susceptibility to lethal infection with H1N1 CA04 influenza virus, and moreover that survival was dependent on the presence of IL-5. The beneficial effects of IFN-gamma neutralization were not observed in ILC2-deficient animals. These data support the novel concept that IFN-gamma can have a detrimental role in the pathogenesis of influenza through a restriction in ILC2 activity. Thus, regulation of ILC2 activity is a potential target for post-infection therapy of influenza. |
