tetano
Editor, Senior Moderator
J Immunol. 2018 May 30. pii: ji1701796. doi: 10.4049/jimmunol.1701796. [Epub ahead of print]
[h=1]IL-36γ Protects against Severe Influenza Infection by Promoting Lung Alveolar Macrophage Survival and Limiting Viral Replication.[/h] Wein AN[SUP]1[/SUP], Dunbar PR[SUP]1[/SUP], McMaster SR[SUP]1[/SUP], Li ZT[SUP]1[/SUP], Denning TL[SUP]2[/SUP], Kohlmeier JE[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Although influenza virus infection remains a concerning disease for public health, the roles of individual cytokines during the immune response to influenza infection are not fully understood. We have identified IL-36γ as a key mediator of immune protection during both high- and low-pathogenesis influenza infection. Il36g mRNA is upregulated in the lung following influenza infection, and mice lacking IL-36γ have greatly increased morbidity and mortality upon infection with either H1N1 or H3N2 influenza. The increased severity of influenza infection in IL-36γ-knockout (KO) mice is associated with increased viral titers, higher levels of proinflammatory cytokines early in infection, and more diffuse pathologic conditions late in the disease course. Interestingly, the increased severity of disease in IL-36γ-KO mice correlates with a rapid loss of alveolar macrophages following infection. We find that the alveolar macrophages from naive IL-36γ-KO mice have higher expression of M2-like surface markers compared with wild-type (WT) mice and show increased apoptosis within 24 h of infection. Finally, transfer of WT alveolar macrophages to IL-36γ-KO mice restores protection against lethal influenza challenge to levels observed in WT mice. Together, these data identify a critical role for IL-36γ in immunity against influenza virus and demonstrate the importance of IL-36γ signaling for alveolar macrophage survival during infection.
PMID: 29848754 DOI: 10.4049/jimmunol.1701796
[h=1]IL-36γ Protects against Severe Influenza Infection by Promoting Lung Alveolar Macrophage Survival and Limiting Viral Replication.[/h] Wein AN[SUP]1[/SUP], Dunbar PR[SUP]1[/SUP], McMaster SR[SUP]1[/SUP], Li ZT[SUP]1[/SUP], Denning TL[SUP]2[/SUP], Kohlmeier JE[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Although influenza virus infection remains a concerning disease for public health, the roles of individual cytokines during the immune response to influenza infection are not fully understood. We have identified IL-36γ as a key mediator of immune protection during both high- and low-pathogenesis influenza infection. Il36g mRNA is upregulated in the lung following influenza infection, and mice lacking IL-36γ have greatly increased morbidity and mortality upon infection with either H1N1 or H3N2 influenza. The increased severity of influenza infection in IL-36γ-knockout (KO) mice is associated with increased viral titers, higher levels of proinflammatory cytokines early in infection, and more diffuse pathologic conditions late in the disease course. Interestingly, the increased severity of disease in IL-36γ-KO mice correlates with a rapid loss of alveolar macrophages following infection. We find that the alveolar macrophages from naive IL-36γ-KO mice have higher expression of M2-like surface markers compared with wild-type (WT) mice and show increased apoptosis within 24 h of infection. Finally, transfer of WT alveolar macrophages to IL-36γ-KO mice restores protection against lethal influenza challenge to levels observed in WT mice. Together, these data identify a critical role for IL-36γ in immunity against influenza virus and demonstrate the importance of IL-36γ signaling for alveolar macrophage survival during infection.
PMID: 29848754 DOI: 10.4049/jimmunol.1701796