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Amino acids 89–96 of Salmonella typhimurium flagellin represent the major domain responsible for TLR5-independent adjuvanticity in the humoral immune response

Cellular & Molecular Immunology volume 12, pages 625–632 (2015)Cite this article

Abstract

Toll-like receptor 5 (TLR5) signaling in response to flagellin is dispensable for inducing humoral immunity, but alterations of aa 89–96, the TLR5 binding site, significantly reduced the adjuvanticity of flagellin. These observations indicate that the underlying mechanism remains incompletely understood. Here, we found that the native form of Salmonella typhimurium aa 89–96-mutant flagellin extracted from flagella retains some TLR5 recognition activity, indicating that aa 89–96 is the primary, but not the only site that imparts TLR5 activity. Additionally, this mutation impaired the production of IL-1β and IL-18. Using TLR5KO mice, we found that aa 89–96 is critical for the humoral adjuvant effect, but this effect was independent of TLR5 activation triggered by this region of flagellin. In summary, our findings suggest that aa 89–96 of flagellin is not only the crucial site responsible for TLR5 recognition, but is also important for humoral immune adjuvanticity through a TLR5-independent pathway.

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Acknowledgements

This work was supported by the National Basic Research Program of China (2012CB518805), the National Natural Science Foundation of China (31230070, 31172299), the Program for New Century Excellent Talents in University (NCET-12-0745) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). We thank XiaoMing Zhang of Institut Pasteur in Paris for assistance with in vivo studies and for critically reading this manuscript, and Edith Deriaud of Institut Pasteur in Paris for technical assistance.

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Author notes

  1. Dr XA Jiao, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, China. E-mail: jiao@yzu.edu.cn

Authors and Affiliations

  1. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, China

    Lei Zhang, Zhiming Pan, Xilong Kang, Yun Yang, Na Zhang & Xinan Jiao

  2. Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China

    Lei Zhang, Zhiming Pan, Xilong Kang, Yun Yang, Na Zhang & Xinan Jiao

  3. Ministry of Education Key Lab for Avian Preventive Medicine, Yangzhou University, Yangzhou, China

    Lei Zhang, Zhiming Pan & Xinan Jiao

  4. Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Lei Zhang, Heekap Kang & James M Rosati

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  1. Lei Zhang
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Zhang, L., Pan, Z., Kang, X. et al. Amino acids 89–96 of Salmonella typhimurium flagellin represent the major domain responsible for TLR5-independent adjuvanticity in the humoral immune response. Cell Mol Immunol 12, 625–632 (2015). https://doi.org/10.1038/cmi.2014.76

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