@article{cec4ed709a584da2b39d6087c78e1d57,
title = "The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock",
abstract = "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.",
keywords = "Antimicrobial proteins, circadian clock, feeding rhythms, foodborne pathogen, innate immunity, innate lymphoid cells, intestine, microbiota",
author = "Brooks, {John F.} and Behrendt, {Cassie L.} and Ruhn, {Kelly A.} and Syann Lee and Prithvi Raj and Takahashi, {Joseph S.} and Hooper, {Lora V.}",
note = "Funding Information: We thank Brian Hassell, Madison Spence, and Nicole Salinas for assistance with mouse experiments and Phoebe Doss, Robyn Leidel, Rebecca Jackson, and Dr. Anza Darehshouri for assistance with electron microscopy. We thank Dr. Andrew Gewirtz (Georgia State University) for providing the SFB used in the monocolonization experiments. Part of the graphical abstract was created at Biorender.com . The Zeiss Sigma scanning electron microscope was purchased with the NIH Shared Instrumentation program grant 1S10OD020103-01 to Dr. Katherine Luby-Phelps. This work was supported by NIH grant R01 DK070855 (L.V.H.), a Welch Foundation grant ( I-1874 to L.V.H.), and the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases (L.V.H.). J.F.B. was supported by NIH grant T32 AI005284 and a Howard Hughes Medical Institute Hanna Gray Fellowship . L.V.H. and J.S.T. are Investigators of the Howard Hughes Medical Institute. Funding Information: We thank Brian Hassell, Madison Spence, and Nicole Salinas for assistance with mouse experiments and Phoebe Doss, Robyn Leidel, Rebecca Jackson, and Dr. Anza Darehshouri for assistance with electron microscopy. We thank Dr. Andrew Gewirtz (Georgia State University) for providing the SFB used in the monocolonization experiments. Part of the graphical abstract was created at Biorender.com. The Zeiss Sigma scanning electron microscope was purchased with the NIH Shared Instrumentation program grant 1S10OD020103-01 to Dr. Katherine Luby-Phelps. This work was supported by NIH grant R01 DK070855 (L.V.H.), a Welch Foundation grant (I-1874 to L.V.H.), and the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases (L.V.H.). J.F.B. was supported by NIH grant T32 AI005284 and a Howard Hughes Medical Institute Hanna Gray Fellowship. L.V.H. and J.S.T. are Investigators of the Howard Hughes Medical Institute. J.F.B. designed and performed most experiments. C.L.B. performed experiments in germ-free mice. K.A.R. provided technical assistance with mouse experiments. S.L. helped with the metabolic cage studies. P.R. performed the 16S rRNA analysis. J.S.T. provided the Clock?19/?19 mice and advised on experimental interpretation. J.F.B. and L.V.H. designed experiments, interpreted results, and wrote the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = aug,
day = "5",
doi = "10.1016/j.cell.2021.07.001",
language = "English (US)",
volume = "184",
pages = "4154--4167.e12",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "16",
}