Circadian clock regulates the host response to Salmonella

Marina M. Bellet, Elisa Deriu, Janet Z. Liu, Benedetto Grimaldi, Christoph Blaschitz, Michael Zeller, Robert A. Edwards, Saurabh Sahar, Satya Dandekar, Pierre Baldi, Michael D. George, Manuela Raffatellu, Paolo Sassone-Corsia

Research output: Contribution to journalArticle

111 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9897-9902
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number24
DOIs
StatePublished - Jun 11 2013

Keywords

  • Clock genes
  • Gastroenteritis
  • Inflammation
  • Intestine
  • Microbes

ASJC Scopus subject areas

  • General

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    Bellet, M. M., Deriu, E., Liu, J. Z., Grimaldi, B., Blaschitz, C., Zeller, M., Edwards, R. A., Sahar, S., Dandekar, S., Baldi, P., George, M. D., Raffatellu, M., & Sassone-Corsia, P. (2013). Circadian clock regulates the host response to Salmonella. Proceedings of the National Academy of Sciences of the United States of America, 110(24), 9897-9902. https://doi.org/10.1073/pnas.1120636110