Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis.

Cell host & microbe 2023 Jun 14

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Commensal bacteria are critically involved in the establishment of tolerance against inflammatory challenges, the molecular mechanisms of which are just being uncovered. All kingdoms of life produce aminoacyl-tRNA synthetases (ARSs). Thus far, the non-translational roles of ARSs have largely been reported in eukaryotes. Here, we report that the threonyl-tRNA synthetase (AmTARS) of the gut-associated bacterium Akkermansia muciniphila is secreted and functions to monitor and modulate immune homeostasis. Secreted AmTARS triggers M2 macrophage polarization and orchestrates the production of anti-inflammatory IL-10 via its unique, evolutionary-acquired regions, which mediates specific interactions with TLR2. This interaction activates the MAPK and PI3K/AKT signaling pathways, which converge on CREB, leading to an efficient production of IL-10 and suppression of the central inflammatory mediator NF-κB. AmTARS restores IL-10-positive macrophages, increases IL-10 levels in the serum, and attenuates the pathological effects in colitis mice. Thus, commensal tRNA synthetases can act as intrinsic mediators that maintain homeostasis. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Su-Man Kim, Shinhye Park, Seung-Ho Hwang, Eun-Young Lee, Jong-Hwan Kim, Ga Seul Lee, Giljae Lee, Dong-Ho Chang, Jae-Geun Lee, Jungwon Hwang, Youngjin Lee, Minsoo Kyung, Eun-Kyoung Kim, Jae-Hoon Kim, Tae-Hwan Kim, Jeong Hee Moon, Byoung-Chan Kim, GwangPyo Ko, Seon-Young Kim, Ji-Hwan Ryu, Jeong-Soo Lee, Chul-Ho Lee, Jeong-Yoon Kim, Sunghoon Kim, Won-Jae Lee, Myung Hee Kim. Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis. Cell host & microbe. 2023 Jun 14;31(6):1021-1037.e10