%0 Figure %A Gopal, Radha %A Lee, Benjamin %A J. McHugh, Kevin %A Rich, Helen E. %A Ramanan, Krishnaveni %A Mandalapu, Sivanarayana %A Clay, Michelle E. %A Seger, Philip J. %A I. Enelow, Richard %A Manni, Michelle L. %A Robinson, Keven M. %A Rangel-Moreno, Javier %A F. Alcorn, John %D 2018 %T Image_5_STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection.TIFF %U https://frontiersin.figshare.com/articles/figure/Image_5_STAT2_Signaling_Regulates_Macrophage_Phenotype_During_Influenza_and_Bacterial_Super-Infection_TIFF/7126496 %R 10.3389/fimmu.2018.02151.s005 %2 https://frontiersin.figshare.com/ndownloader/files/13111796 %K influenza %K Staphylococcus aureus %K super-infection %K STAT2 %K macrophages %K lung %K pneumonia %X

Influenza is a common respiratory virus that infects between 5 and 20% of the US population and results in 30,000 deaths annually. A primary cause of influenza-associated death is secondary bacterial pneumonia. We have previously shown that influenza induces type I interferon (IFN)-mediated inhibition of Type 17 immune responses, resulting in exacerbation of bacterial burden during influenza and Staphylococcus aureus super-infection. In this study, we investigated the role of STAT2 signaling during influenza and influenza-bacterial super-infection in mice. Influenza-infected STAT2−/− mice had increased morbidity, viral burden, and inflammation when compared to wild-type mice. Despite an exaggerated inflammatory response to influenza infection, we found increased bacterial control and survival in STAT2 deficient mice during influenza-MRSA super-infection compared to controls. Further, we found that increased bacterial clearance during influenza-MRSA super-infection is not due to rescue of Type 17 immunity. Absence of STAT2 was associated with increased accumulation of M1, M2 and M1/M2 co-expressing macrophages during influenza-bacterial super-infection. Neutralization of IFNγ (M1) and/or Arginase 1 (M2) impaired bacterial clearance in Stat2−/− mice during super-infection, demonstrating that pulmonary macrophages expressing a mixed M1/M2 phenotype promote bacterial control during influenza-bacterial super-infection. Together, these results suggest that the STAT2 signaling is involved in suppressing macrophage activation and bacterial control during influenza-bacterial super-infection. Further, these studies reveal novel mechanistic insight into the roles of macrophage subpopulations in pulmonary host defense.

%I Frontiers