[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.14348/molcells.2020.2300

Flagellin-Stimulated Production of Interferon-β Promotes Anti-Flagellin IgG2c and IgA Responses

Kang, Wondae (Division of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology)
Park, Areum (Division of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology)
Huh, Ji-Won (Division of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology)
You, Gihoon (Division of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology)
Jung, Da-Jung (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)
Song, Manki (International Vaccine Institute)
Lee, Heung Kyu (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)
Kim, You-Me (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)

Abstract

Flagellin, a major structural protein of the flagellum found in all motile bacteria, activates the TLR5- or NLRC4 inflammasome-dependent signaling pathway to induce innate immune responses. Flagellin can also serve as a specific antigen for the adaptive immune system and stimulate anti-flagellin antibody responses. Failure to recognize commensal-derived flagellin in TLR5-deficient mice leads to the reduction in anti-flagellin IgA antibodies at steady state and causes microbial dysbiosis and mucosal barrier breach by flagellated bacteria to promote chronic intestinal inflammation. Despite the important role of anti-flagellin antibodies in maintaining the intestinal homeostasis, regulatory mechanisms underlying the flagellin-specific antibody responses are not well understood. In this study, we show that flagellin induces interferon-β (IFN-β) production and subsequently activates type I IFN receptor signaling in a TLR5- and MyD88-dependent manner in vitro and in vivo. Internalization of TLR5 from the plasma membrane to the acidic environment of endolysosomes was required for the production of IFN-β, but not for other pro-inflammatory cytokines. In addition, we found that anti-flagellin IgG2c and IgA responses were severely impaired in interferon-alpha receptor 1 (IFNAR1)-deficient mice, suggesting that IFN-β produced by the flagellin stimulation regulates anti-flagellin antibody class switching. Our findings shed a new light on the regulation of flagellin-mediated immune activation and may help find new strategies to promote the intestinal health and develop mucosal vaccines.

Keywords

anti-flagellin antibody; flagellin; IgA; interferon- ${\beta}$ ; Toll-like receptor 5;

Citations & Related Records

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