Mycobacterial mycolic acids trigger inhibitory receptor Clec12A to suppress host immune responses

Naoya Nishimura, Noriyuki Tomiyasu, Shota Torigoe, Satoru Mizuno, Hanako Fukano, Eri Ishikawa, Harutaka Katano, Yoshihiko Hoshino, Kazuhiro Matsuo, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Koichi Akashi, Sho Yamasaki

研究成果: ジャーナルへの寄稿学術誌査読

5 被引用数 (Scopus)

抄録

Mycobacteria often cause chronic infection. To establish persistence in the host, mycobacteria need to evade host immune responses. However, the molecular mechanisms underlying the evasion strategy are not fully understood. Here, we demonstrate that mycobacterial cell wall lipids trigger an inhibitory receptor to suppress host immune responses. Mycolic acids are major cell wall components and are essential for survival of mycobacteria. By screening inhibitory receptors that react with mycobacterial lipids, we found that mycolic acids from various mycobacterial species bind to mouse Clec12A, and more potently to human Clec12A. Clec12A is a conserved inhibitory C-type lectin receptor containing immunoreceptor tyrosine-based inhibitory motif (ITIM). Innate immune responses, such as MCP-1 production, and PPD-specific recall T cell responses were augmented in Clec12A-deficient mice after infection. In contrast, human Clec12A transgenic mice were susceptible to infection with M. tuberculosis. These results suggest that mycobacteria dampen host immune responses by hijacking an inhibitory host receptor through their specific and essential lipids, mycolic acids. The blockade of this interaction might provide a therapeutic option for the treatment or prevention of mycobacterial infection.

本文言語英語
論文番号102294
ジャーナルTuberculosis
138
DOI
出版ステータス出版済み - 1月 2023

!!!All Science Journal Classification (ASJC) codes

  • 微生物学
  • 免疫学
  • 微生物学(医療)
  • 感染症

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