microbiology-reproductive-health-2017-posters-abstracts

Page 45

International Congress on

Annual Summit on

October 02-03, 2017 Atlanta,USA

Microbiology and Pharmaceutical Microbiology

Sexual & Reproductive Health

Journal of sexual and Reproductive medicine | Volume.1, Issue.2

Influenza A virus-induced IL-6 storm is regulated by SOCS3

Ji-Long Chen

1, 2

, Ruoxiang Yan

, Jing Ouyang

, Biao Chen

and

Xiancheng Zeng

Fujian Agriculture and Forestry University, China

Chinese Academy of Sciences, Beijing, China

nfluenza A virus (IAV) is still a major public health threat in the world, as indicated by enormous severe

pneumonia resulted from the virus infection every year. IL-6-involved excessive inflammatory response to IAV

infection profoundly contributes to IAV pathogenesis. However, precise regulatory mechanisms underlying such

a response are poorly understood. Here we found from both

in vivo

and

in vitro

studies that IAV not only induced

surge of IL-6 release, but also greatly upregulated expression of SOCS3, the potent suppressor of IL-6/STAT3

signaling. Interestingly, there existed a cytokine-independent mechanism of the robust induction of SOCS3

by IAV at least at early stage of the infection. Furthermore, we generated SOCS3-knockdown transgenic mice

(TG), and surprisingly observed from virus challenge experiments using the TG mice that disruption of SOCS3

expression provided significant protection against IAV infection, as evidenced by attenuated acute lung injury, a

higher survival rate of infected animals and lower viral load in infected tissues as compared with those of wild-

type littermates under same challenge. The activity of NFκB and the expression of its target gene IL-6 were

remarkably suppressed in SOCS3-knockdown A549 cells and TG mice after infection with IAV. Moreover, we

defined that enhanced STAT3 activity caused by SOCS3 silencing was important for the negative regulation of

NFκB and IL-6. These findings establish a critical role for IL-6-STAT3-SOCS3 axis in the pathogenesis of IAV,

and suggest that influenza virus has evolved a strategy to circumvent IL-6/STAT3-mediated immune response

through upregulating SOCS3.