title: Circadian clock regulates the host response to Salmonella.
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.
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, Institute for Immunology, School of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Marina M
authors.initials: MM
authors.lastname: Bellet
authors.forename: Elisa
authors.initials: E
authors.lastname: Deriu
authors.forename: Janet Z
authors.initials: JZ
authors.lastname: Liu
authors.forename: Benedetto
authors.initials: B
authors.lastname: Grimaldi
authors.forename: Christoph
authors.initials: C
authors.lastname: Blaschitz
authors.forename: Michael
authors.initials: M
authors.lastname: Zeller
authors.forename: Robert A
authors.initials: RA
authors.lastname: Edwards
authors.forename: Saurabh
authors.initials: S
authors.lastname: Sahar
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.forename: Michael D
authors.initials: MD
authors.lastname: George
authors.forename: Manuela
authors.initials: M
authors.lastname: Raffatellu
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D002432:Cecum / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D057906:Circadian Clocks / Q000235:genetics / Q000276:immunology*; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology* / Q000502:physiology; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D056926:CLOCK Proteins; C538944:Clock protein, mouse
keywords: clock genes; gastroenteritis; inflammation; intestine; microbes