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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 251 - 263 (13page)
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초록· 키워드
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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 antiflagellin 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 proinflammatory cytokines. In addition, we found that antiflagellin 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.
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참고문헌 (58)
참고문헌 신청
Adachi, O. / 1998 / Targeted disruption of the MyD88 gene results in loss of IL-1-and IL-18-mediated function / Immunity 9:143~150
Atif, S. M. / 2015 / Rapid CD4(+)T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9 / Eur. J. Immunol 45:513~524
Aubry, C. / 2012 / Both TLR2 and TRIF contribute to interferon-beta production during Listeria infection / PLoS One 7:e33299
Carvalho, F. A. / 2012 / Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice / Cell Host Microbe 12:139~152
Choi, Y. J. / 2010 / TRIF mediates toll-like receptor 5-induced signaling in intestinal epithelial cells / J. Biol. Chem 285:37570~37578
Atif, S. M. / 2015 / Rapid CD4(+)T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9 / Eur. J. Immunol 45:513~524
Aubry, C. / 2012 / Both TLR2 and TRIF contribute to interferon-beta production during Listeria infection / PLoS One 7:e33299
Carvalho, F. A. / 2012 / Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice / Cell Host Microbe 12:139~152
Choi, Y. J. / 2010 / TRIF mediates toll-like receptor 5-induced signaling in intestinal epithelial cells / J. Biol. Chem 285:37570~37578
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