Circadian clock regulates the host response to Salmonella

• Published in: Proceedings of the National Academy of Sciences - PNAS 2013-06, Vol.110 (24), p.9897-9902
• Main Authors: Bellet, Marina M., Deriu, Elisa, Liu, Janet Z., Grimaldi, Benedetto, Blaschitz, Christoph, Zeller, Michael, Edwards, Robert A., Sahar, Saurabh, Dandekar, Satya, Baldi, Pierre, George, Michael D., Raffatellu, Manuela, Sassone-Corsi, Paolo
• Format: Article
• Language: English
• Subjects: acute course; Animals; Antimicrobials; Biological Sciences; Cecum - immunology; Cecum - metabolism; Cecum - microbiology; Cells, Cultured; Circadian Clocks - genetics; Circadian Clocks - immunology; Circadian rhythm; CLOCK Proteins - deficiency; CLOCK Proteins - genetics; CLOCK Proteins - immunology; Cluster Analysis; Cytokines; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; Datasets; enteropathogens; Gene Expression Profiling; Gene expression regulation; Gene Regulatory Networks - genetics; Gene Regulatory Networks - immunology; Genes; Host-Pathogen Interactions - immunology; immune response; Immune system; Infections; infectious diseases; Inflammation; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Lipopolysaccharides - immunology; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Salmonella; Salmonella Infections, Animal - genetics; Salmonella Infections, Animal - immunology; Salmonella Infections, Animal - microbiology; Salmonella Typhimurium; Salmonella typhimurium - immunology; Salmonella typhimurium - physiology; Secretion; Time Factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1120636110

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.