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Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9897-902. doi: 10.1073/pnas.1120636110. Epub 2013 May 28.

Circadian clock regulates the host response to Salmonella.

Author information

1
Center for Epigenetics and Metabolism, Department of Biological Chemistry, Institute for Immunology, School of Medicine, University of California, Irvine, CA 92697, USA.

Abstract

Organisms adapt to day-night cycles through highly specialized circadian machinery, whose molecular components anticipate and drive changes in organism behavior and metabolism. Although many effectors of the immune system are known to follow daily oscillations, the role of the circadian clock in the immune response to acute infections is not understood. Here we show that the circadian clock modulates the inflammatory response during acute infection with the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). Mice infected with S. Typhimurium were colonized to higher levels and developed a higher proinflammatory response during the early rest period for mice, compared with other times of the day. We also demonstrate that a functional clock is required for optimal S. Typhimurium colonization and maximal induction of several proinflammatory genes. These findings point to a clock-regulated mechanism of activation of the immune response against an enteric pathogen and may suggest potential therapeutic strategies for chronopharmacologic interventions.

KEYWORDS:

clock genes; gastroenteritis; inflammation; intestine; microbes

PMID:
23716692
PMCID:
PMC3683799
DOI:
10.1073/pnas.1120636110
[Indexed for MEDLINE]
Free PMC Article

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