tetano
Editor, Senior Moderator
Front Immunol. 2018 Sep 25;9:2151. doi: 10.3389/fimmu.2018.02151. eCollection 2018.
[h=1]STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection.[/h] Gopal R[SUP]1[/SUP], Lee B[SUP]2[/SUP], McHugh KJ[SUP]1[/SUP], Rich HE[SUP]1[/SUP], Ramanan K[SUP]1[/SUP], Mandalapu S[SUP]1[/SUP], Clay ME[SUP]1[/SUP], Seger PJ[SUP]1[/SUP], Enelow RI[SUP]3[/SUP], Manni ML[SUP]1[/SUP], Robinson KM[SUP]4[/SUP], Rangel-Moreno J[SUP]5[/SUP], Alcorn JF[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] STAT2; Staphylococcus aureus; influenza; lung; macrophages; pneumonia; super-infection
PMID: 30337919 PMCID: PMC6178135 DOI: 10.3389/fimmu.2018.02151
[h=1]STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection.[/h] Gopal R[SUP]1[/SUP], Lee B[SUP]2[/SUP], McHugh KJ[SUP]1[/SUP], Rich HE[SUP]1[/SUP], Ramanan K[SUP]1[/SUP], Mandalapu S[SUP]1[/SUP], Clay ME[SUP]1[/SUP], Seger PJ[SUP]1[/SUP], Enelow RI[SUP]3[/SUP], Manni ML[SUP]1[/SUP], Robinson KM[SUP]4[/SUP], Rangel-Moreno J[SUP]5[/SUP], Alcorn JF[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] STAT2; Staphylococcus aureus; influenza; lung; macrophages; pneumonia; super-infection
PMID: 30337919 PMCID: PMC6178135 DOI: 10.3389/fimmu.2018.02151