Gopal, Radha Lee, Benjamin J. McHugh, Kevin Rich, Helen E. Ramanan, Krishnaveni Mandalapu, Sivanarayana Clay, Michelle E. Seger, Philip J. I. Enelow, Richard Manni, Michelle L. Robinson, Keven M. Rangel-Moreno, Javier F. Alcorn, John Image_1_STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection.TIFF <p>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<sup>−/−</sup> 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<sup>−/−</sup> 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.</p> influenza;Staphylococcus aureus;super-infection;STAT2;macrophages;lung;pneumonia 2018-09-25
    https://frontiersin.figshare.com/articles/figure/Image_1_STAT2_Signaling_Regulates_Macrophage_Phenotype_During_Influenza_and_Bacterial_Super-Infection_TIFF/7126484
10.3389/fimmu.2018.02151.s001