Circadian clock regulates the host response to Salmonella

• DOI: 10.1073/pnas.1120636110
• Publication Date: 2013-05-29T05:46:29Z
• Authors: 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-Corsi
• Keywords: Lipopolysaccharides; Salmonella typhimurium; 0301 basic medicine; Time Factors; CLOCK Proteins; Mice; 03 medical and health sciences; Circadian Clocks; Animals; Cluster Analysis; Gene Regulatory Networks; Clock genes; Cecum; Cells, Cultured; Oligonucleotide Array Sequence Analysis; Inflammation; Mice, Knockout; Salmonella Infections, Animal; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; Macrophages; Gastroenteritis; Intestine; 3. Good health; Mice, Inbred C57BL; Microbes; Host-Pathogen Interactions; Cytokines; Inflammation Mediators

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.