STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection.
STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection.
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DOI：
10.3389/fimmu.2018.02151
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发表时间：
2018
影响因子：
7.3
通讯作者：
Alcorn JF
中科院分区：
文献类型：
--
作者：
Gopal R;Lee B;McHugh KJ;Rich HE;Ramanan K;Mandalapu S;Clay ME;Seger PJ;Enelow RI;Manni ML;Robinson KM;Rangel-Moreno J;Alcorn JF
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.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.3
作者：
BRACIALE, TJ
通讯作者：
BRACIALE, TJ
影响因子：
5.7
作者：
Dussurget O;Bierne H;Cossart P
通讯作者：
Cossart P
影响因子：
13
作者：
Kolls, Jay K.;Khader, Shabaana A.
通讯作者：
Khader, Shabaana A.
DOI：
10.4049/jimmunol.0900995
发表时间：
2009-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Crowe CR;Chen K;Pociask DA;Alcorn JF;Krivich C;Enelow RI;Ross TM;Witztum JL;Kolls JK
通讯作者：
Kolls JK