tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2022 Feb 22;119(8):e2118535119.
doi: 10.1073/pnas.2118535119.
Viral PB1-F2 and host IFN-γ guide ILC2 and T cell activity during influenza virus infection
Tarani Kanta Barman[SUP] 1 [/SUP], Victor C Huber[SUP] 2 [/SUP], Jesse L Bonin[SUP] 1 [/SUP], Danielle Califano[SUP] 1 [/SUP], Sharon L Salmon[SUP] 1 [/SUP], Andrew N J McKenzie[SUP] 3 [/SUP], Dennis W Metzger[SUP] 4 [/SUP]
Affiliations
Abstract
Functional plasticity of innate lymphoid cells (ILCs) and T cells is regulated by host environmental cues, but the influence of pathogen-derived virulence factors has not been described. We now report the interplay between host interferon (IFN)-γ and viral PB1-F2 virulence protein in regulating the functions of ILC2s and T cells that lead to recovery from influenza virus infection of mice. In the absence of IFN-γ, lung ILC2s from mice challenged with the A/California/04/2009 (CA04) H1N1 virus, containing nonfunctional viral PB1-F2, initiated a robust IL-5 response, which also led to improved tissue integrity and increased survival. Conversely, challenge with Puerto Rico/8/1934 (PR8) H1N1 virus expressing fully functional PB1-F2, suppressed IL-5[SUP]+[/SUP] ILC2 responses, and induced a dominant IL-13[SUP]+[/SUP] CD8 T cell response, regardless of host IFN-γ expression. IFN-γ-deficient mice had increased survival and improved tissue integrity following challenge with lethal doses of CA04, but not PR8 virus, and increased resistance was dependent on the presence of IFN-γR[SUP]+[/SUP] ILC2s. Reverse-engineered influenza viruses differing in functional PB1-F2 activity induced ILC2 and T cell phenotypes similar to the PB1-F2 donor strains, demonstrating the potent role of viral PB1-F2 in host resistance. These results show the ability of a pathogen virulence factor together with host IFN-γ to regulate protective pulmonary immunity during influenza infection.
Keywords: IFN-γ; ILCs; PB1-F2; T cells; influenza.
. 2022 Feb 22;119(8):e2118535119.
doi: 10.1073/pnas.2118535119.
Viral PB1-F2 and host IFN-γ guide ILC2 and T cell activity during influenza virus infection
Tarani Kanta Barman[SUP] 1 [/SUP], Victor C Huber[SUP] 2 [/SUP], Jesse L Bonin[SUP] 1 [/SUP], Danielle Califano[SUP] 1 [/SUP], Sharon L Salmon[SUP] 1 [/SUP], Andrew N J McKenzie[SUP] 3 [/SUP], Dennis W Metzger[SUP] 4 [/SUP]
Affiliations
- PMID: 35169077
- DOI: 10.1073/pnas.2118535119
Abstract
Functional plasticity of innate lymphoid cells (ILCs) and T cells is regulated by host environmental cues, but the influence of pathogen-derived virulence factors has not been described. We now report the interplay between host interferon (IFN)-γ and viral PB1-F2 virulence protein in regulating the functions of ILC2s and T cells that lead to recovery from influenza virus infection of mice. In the absence of IFN-γ, lung ILC2s from mice challenged with the A/California/04/2009 (CA04) H1N1 virus, containing nonfunctional viral PB1-F2, initiated a robust IL-5 response, which also led to improved tissue integrity and increased survival. Conversely, challenge with Puerto Rico/8/1934 (PR8) H1N1 virus expressing fully functional PB1-F2, suppressed IL-5[SUP]+[/SUP] ILC2 responses, and induced a dominant IL-13[SUP]+[/SUP] CD8 T cell response, regardless of host IFN-γ expression. IFN-γ-deficient mice had increased survival and improved tissue integrity following challenge with lethal doses of CA04, but not PR8 virus, and increased resistance was dependent on the presence of IFN-γR[SUP]+[/SUP] ILC2s. Reverse-engineered influenza viruses differing in functional PB1-F2 activity induced ILC2 and T cell phenotypes similar to the PB1-F2 donor strains, demonstrating the potent role of viral PB1-F2 in host resistance. These results show the ability of a pathogen virulence factor together with host IFN-γ to regulate protective pulmonary immunity during influenza infection.
Keywords: IFN-γ; ILCs; PB1-F2; T cells; influenza.