期刊
CELL
卷 184, 期 16, 页码 4154-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.07.001
关键词
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资金
- NIH [T32 AI005284, 1S10OD02010301, R01 DK070855]
- Welch Foundation [R01 DK070855, I-1874]
- Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases
- Howard Hughes Medical Institute Hanna Gray Fellowship
The study found that the intestinal microbiota generates diurnal rhythms in innate immunity that synchronize with feeding rhythms to anticipate microbial exposure. This synchronization activates an immunological circuit triggering oscillations in epithelial STAT3 expression and activation that produce rhythmic antimicrobial protein expression, causing resistance to bacterial infection to vary across the day-night cycle.
Environmental light cycles entrain circadian feeding behaviors in animals that produce rhythms in exposure to foodborne bacteria. Here, we show that the intestinal microbiota generates diurnal rhythms in innate immunity that synchronize with feeding rhythms to anticipate microbial exposure. Rhythmic expression of antimicrobial proteins was driven by daily rhythms in epithelial attachment by segmented filamentous bacteria (SFB), members of the mouse intestinal microbiota. Rhythmic SFB attachment was driven by the circadian clock through control of feeding rhythms. Mechanistically, rhythmic SFB attachment activated an immunological circuit involving group 3 innate lymphoid cells. This circuit triggered oscillations in epithelial STAT3 expression and activation that produced rhythmic antimicrobial protein expression and caused resistance to Salmonella Typhimurium infection to vary across the day-night cycle. Thus, host feeding rhythms synchronize with the microbiota to promote rhythms in intestinal innate immunity that anticipate exogenous microbial exposure.
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