| RRC ID |
80632
|
| Author |
Nishimura N, Tomiyasu N, Torigoe S, Mizuno S, Fukano H, Ishikawa E, Katano H, Hoshino Y, Matsuo K, Takahashi M, Izumi Y, Bamba T, Akashi K, Yamasaki S.
|
| Title |
Mycobacterial mycolic acids trigger inhibitory receptor Clec12A to suppress host immune responses.
|
| Journal |
Tuberculosis (Edinb)
|
| 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.
|
| Volume |
138
|
| Pages |
102294
|
| Published |
2023-1-1
|
| DOI |
10.1016/j.tube.2022.102294
|
| PII |
S1472-9792(22)00131-7
|
| PMID |
36542980
|
| MeSH |
Animals
Cell Wall / metabolism
Humans
Immunity, Innate
Lectins, C-Type / genetics
Lectins, C-Type / metabolism
Mice
Mycobacterium Infections*
Mycobacterium tuberculosis*
Mycolic Acids / metabolism
Receptors, Mitogen / metabolism
|
| Resource |
| General Microbes |
JCM 6390
JCM 15900
JCM 6387
JCM 5876
JCM 13575
JCM 6366
JCM 6363
JCM 5865
JCM 12143
JCM 15661
JCM 14744
JCM 13390
JCM 6384
JCM 15465
JCM 12407
JCM 6379
JCM 6383
JCM 6382 |
