10.3389/fimmu.2018.02151.s004 Radha Gopal Radha Gopal Benjamin Lee Benjamin Lee Kevin J. McHugh Kevin J. McHugh Helen E. Rich Helen E. Rich Krishnaveni Ramanan Krishnaveni Ramanan Sivanarayana Mandalapu Sivanarayana Mandalapu Michelle E. Clay Michelle E. Clay Philip J. Seger Philip J. Seger Richard I. Enelow Richard I. Enelow Michelle L. Manni Michelle L. Manni Keven M. Robinson Keven M. Robinson Javier Rangel-Moreno Javier Rangel-Moreno John F. Alcorn John F. Alcorn Image_4_STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection.TIFF Frontiers 2018 influenza Staphylococcus aureus super-infection STAT2 macrophages lung pneumonia 2018-09-25 04:19:11 Figure https://frontiersin.figshare.com/articles/figure/Image_4_STAT2_Signaling_Regulates_Macrophage_Phenotype_During_Influenza_and_Bacterial_Super-Infection_TIFF/7126493 <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>