title: Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice.
abstract: During colonization of germfree mice with the total fecal microbial community of their conventionally born and raised siblings (conventionalization), the intestinal mucosal immune system initiates and maintains a balanced immune response. However, the genetic regulation of these balanced, appropriate responses to the microbiota is obscure. Here, combined analysis of germfree and conventionalized mice revealed that the major molecular responses could be detected initiating at day 4 post conventionalization, with a strong induction of innate immune functions followed by stimulation of adaptive immune responses and development and expansion of adaptive immune cells at later stages of conventionalization. This study provides a comprehensive overview of mouse developmental and immune-related cellular pathways and processes that were co-mediated by the commensal microbiota and suggests which mechanisms were involved in this reprogramming. The dynamic, region-dependent mucosal responses to the colonizing microbiota revealed potential transcriptional signatures for the control of intestinal homeostasis in healthy mice, which may help to decipher the genetic basis of pathway dysregulation in human intestinal inflammatory diseases.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Sahar
authors.initials: S
authors.lastname: El Aidy
authors.forename: Peter
authors.initials: P
authors.lastname: van Baarlen
authors.forename: Muriel
authors.initials: M
authors.lastname: Derrien
authors.forename: Dicky J
authors.initials: DJ
authors.lastname: Lindenbergh-Kortleve
authors.forename: Guido
authors.initials: G
authors.lastname: Hooiveld
authors.forename: Florence
authors.initials: F
authors.lastname: Levenez
authors.forename: Joël
authors.initials: J
authors.lastname: Doré
authors.forename: Jan
authors.initials: J
authors.lastname: Dekker
authors.forename: Janneke N
authors.initials: JN
authors.lastname: Samsom
authors.forename: Edward E S
authors.initials: EE
authors.lastname: Nieuwenhuis
authors.forename: Michiel
authors.initials: M
authors.lastname: Kleerebezem
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D019295:Computational Biology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D005856:Germ-Free Life; D006706:Homeostasis; D007108:Immune Tolerance; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007422:Intestines / Q000382:microbiology / Q000502:physiology*; D054892:Metagenome / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009928:Organ Specificity; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators; D051192:Receptors, Pattern Recognition