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Activation of NLRC4 downregulates TLR5-mediated antibody immune responses against flagellin

Cellular & Molecular Immunology volume 13, pages 514–523 (2016)Cite this article

Abstract

Bacterial flagellin is a unique pathogen-associated molecular pattern (PAMP), which can be recognized by surface localized Toll-like receptor 5 (TLR5) and the cytosolic NOD-like receptor (NLR) protein 4 (NLRC4) receptors. Activation of the TLR5 and/or NLRC4 signaling pathways by flagellin and the resulting immune responses play important roles in anti-bacterial immunity. However, it remains unclear how the dual activities of flagellin that activate the TLR5 and/or NLRC4 signaling pathways orchestrate the immune responses. In this study, we assessed the effects of flagellin and its mutants lacking the ability to activate TLR5 and NLRC4 alone or in combination on the adaptive immune responses against flagellin. Flagellin that was unable to activate NLRC4 induced a significantly higher antibody response than did wild-type flagellin. The increased antibody response could be eliminated when macrophages were depleted in vivo. The activation of NLRC4 by flagellin downregulated the flagellin-induced and TLR5-mediated immune responses against flagellin.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant numbers 81202381 and 81202312), the National Basic Research Program of China (973 Program) (Grant number 2012CB518904), the National S&T Major Project on Major Infectious Diseases (Grant numbers 2012ZX10001-008 and 2008ZX10001-010) from the Ministry of Science and Technology of the People’s Republic of China. We sincerely thank the Core Facility and Technical Support, Wuhan Institute of Virology and Xuefang An for valuable assistance in the animal studies and Ying Sun, Rong Bao, and Benxia He for their help with the sample collection.

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  1. Dr. Huimin Yan, Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, People’s Republic of China, E-mail: hmyan@wh.iov.cn

  2. Yaoming Li, liym@wh.iov.cn

Authors and Affiliations

  1. Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, People’s Republic of China

    Wei Li, Jingyi Yang, Ejuan Zhang, Maohua Zhong, Yang Xiao, Jie Yu, Dihan Zhou, Yuan Cao, Yi Yang, Yaoming Li & Huimin Yan

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Li, W., Yang, J., Zhang, E. et al. Activation of NLRC4 downregulates TLR5-mediated antibody immune responses against flagellin. Cell Mol Immunol 13, 514–523 (2016). https://doi.org/10.1038/cmi.2015.33

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