Mycobacterial mycolic acids trigger inhibitory receptor Clec12A to suppress host immune responses. (January 2023)

• Record Type: Journal Article
• Authors: Nishimura, Naoya; Tomiyasu, Noriyuki; Torigoe, Shota; Mizuno, Satoru; Fukano, Hanako; Ishikawa, Eri; Katano, Harutaka; Hoshino, Yoshihiko; Matsuo, Kazuhiro; Takahashi, Masatomo; Izumi, Yoshihiro; Bamba, Takeshi; Akashi, Koichi; Yamasaki, Sho
• Is Part Of: Tuberculosis. Volume 138(2022)
• Publication Date: 2023-01
• Subjects: Mycobacteria -- Glycolipids -- Immune evasion -- Host immunity -- C-type lectin receptors; BCG M. bovis bacilli Calmette-Guérin -- BMDC bone marrow-derived dendritic cell -- CLR C-type lectin receptor -- Erdman M. tuberculosis Erdman -- Fr fraction -- HPTLC high performance thin layer chromatography -- H37Rv M. tuberculosis H37Rv -- LTBI latent tuberculosis infection -- Mtb Mycobacterium tuberculosis -- MA mycolic acid -- MSU monosodium urate -- NTM non-tuberculous mycobacteria -- PPD purified protein derivative -- SHP Src homology 2 domain-containing phosphatase -- TDM trehalose dimycolate -- TMM trehalose monomycolate; 616.995
• DOI: 10.1016/j.tube.2022.102294
• Languages: English
• ISSNs: 1472-9792

Abstract

Abstract: 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.