期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 24, 页码 9897-9902出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1120636110
关键词
clock genes; inflammation; gastroenteritis; intestine; microbes
资金
- National Institutes of Health (NIH) [R01-GM081634, LM010235-01A1, 5T15LM007743, T32 AI60573]
- Sirtris Pharmaceuticals, Inc.
- Public Health Service [AI083619, AI083663]
- National Science Foundation [MRI EIA-0321390]
- American Heart Association
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.
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