Oncotarget

Research Papers: Immunology:

RIP3 deficiency ameliorates inflammatory response in mice infected with influenza H7N9 virus infection

Yu-Lin Xu _, Hai-Lin Tang, Hao-Ran Peng, Ping Zhao, Zhong-Tian Qi and Wen Wang

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Oncotarget. 2017; 8:27715-27724. https://doi.org/10.18632/oncotarget.16016

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Abstract

Yu-Lin Xu1,*, Hai-Lin Tang1,*, Hao-Ran Peng1, Ping Zhao1, Zhong-Tian Qi1 and Wen Wang1

1 Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China

* These authors have contributed equally to this study

Correspondence to:

Zhong-Tian Qi, email:

Wen Wang, email:

Keywords: influenza A virus; H7N9 virus; RIP3; necroptosis; proinflammatory cytokines; Immunology and Microbiology Section; Immune response; Immunity

Received: December 08, 2016 Accepted: February 23, 2017 Published: March 08, 2017

Abstract

Influenza H7N9 virus infection causes an acute, highly contagious respiratory illness that triggers cell death of infected cells and airway epithelial destruction. RIP3 is a key regulator of cell death responses to a growing number of viral and microbial agents. This study aimed to investigate the role of RIP3 in inflammation of influenza H7N9 virus infection. Here, RIP3 knock out (RIP3-/-) mice and littermate wild type mice were infected intranasally with influenza H7N9 virus (A/Fujian/S03/2015) to determine the contribution of RIP3 to the inflammatory response of influenza H7N9 virus infection. It was found that RIP3-/- mice infected with H7N9 virus showed higher survival and less weight loss, compared with wild type littermate mice. In addition, RIP3-/- mice had fewer regions of edema, infiltration with inflammatory cells, and alveolar collapses, and the secretions of IL-1β, IL-6, RANTES and MIP-1 in BALF were significantly decreased on days 3 and 7 p.i. when compared with WT mice. Moreover, caspase 1/IL1β signaling was found to be involved in RIP3 associated inflammation of influenza H7N9 virus, but not RIP3/MLKL dependent necrosis. In the conclusion, our results indicated that RIP3 deficiency can protect mice from the infection of influenza H7N9 virus by downregulating caspase 1/IL1β signaling, which provided evidence of the RIP3 involved necroptosis independent manner.


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