Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice

• Published in: Mucosal immunology Vol. 5; no. 5; pp. 567 - 579
• Main Authors: El Aidy, Sahar, van Baarlen, Peter, Derrien, Muriel, Lindenbergh-Kortleve, Dicky J, Hooiveld, Guido, Levenez, Florence, Doré, Joël, Dekker, Jan, Samsom, Janneke N, Nieuwenhuis, Edward E S, Kleerebezem, Michiel
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2012; Elsevier Limited; Nature Pub. Group
• Subjects: 631/250/2152; 631/250/347; 631/443/319/1557; 692/698/2741/2135; Adaptive Immunity; Agricultural sciences; Allergology; Animals; Antibodies; B-Lymphocytes - immunology; B-Lymphocytes - microbiology; bacteria; Bacterial Infections - genetics; Bacterial Infections - immunology; Bacterial Infections - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Differentiation; Cells, Cultured; Computational Biology; Cytokines - genetics; Cytokines - metabolism; defense; expression; Forkhead Transcription Factors - metabolism; Gastroenterology; Gene Expression Profiling; Germ-Free Life; Homeostasis; Immune Tolerance; Immunity, Innate; Immunology; induction; Inflammation Mediators - metabolism; inflammatory-bowel-disease; Intestines - microbiology; Intestines - physiology; Life Sciences; mechanisms; Metagenome - physiology; Mice; Mice, Inbred C57BL; Microarray Analysis; mucins; Organ Specificity; receptors; Receptors, Pattern Recognition - genetics; Receptors, Pattern Recognition - metabolism; responses; t-cell development; T-Lymphocytes - immunology; T-Lymphocytes - microbiology; Up-Regulation; RESPONSES; DEFENSE; MUCINS; BACTERIA; INFLAMMATORY-BOWEL-DISEASE; MECHANISMS; INDUCTION; T-CELL DEVELOPMENT; RECEPTORS; EXPRESSION
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2012.32

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.