Gut archaea drive human MAIT cell responses
Archaea, the third domain of life, are a gut microbiome constituent, but their role in shaping immunity is poorly understood. Mucosal-associated invariant T (MAIT) cells sense microbial metabolites through their T cell receptor and contribute to antimicrobial defence and barrier homeostasis. Key sources of the major MAIT cell antigen 5-OP-RU within the human gut microbiome are unknown. Analysing…
Archaea, a previously understudied third domain of life, are found within the human gut microbiome. However, their impact on the immune system remains unclear. Mucosal-associated invariant T (MAIT) cells play a crucial role in combating germs and maintaining the integrity of the body's protective barriers. These cells identify microbial metabolites through their T cell receptor, contributing significantly to the body's defence mechanisms.
The primary source of MAIT cell antigen 5-OP-RU within the human gut is yet to be identified. Researchers analysed microbiomes from individuals in the UK, Zambia, Kenya, and Uganda. They discovered a strong connection between the presence of archaeal riboflavin biosynthesis and the frequency and activation of MAIT cells in the bloodstream.
Additionally, the levels of 5-OP-RU in stool samples were found to correlate with the abundance of archaea. Cultures of methanogenic archaea, including the human commensal Methanobrevibacter smithii, generated 5-OP-RU, which strongly activated MAIT cells without causing any inflammation. The study reveals that archaea play a pivotal role in shaping human immunity, with important implications for understanding how the microbiome regulates health.
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