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

被引:179
作者
El Aidy, Sahar [1 ,2 ]
van Baarlen, Peter
Derrien, Muriel [1 ,2 ]
Lindenbergh-Kortleve, Dicky J. [3 ]
Hooiveld, Guido [4 ]
Levenez, Florence [5 ]
Dore, Joel [5 ]
Dekker, Jan [1 ,6 ]
Samsom, Janneke N. [3 ]
Nieuwenhuis, Edward E. S. [7 ]
Kleerebezem, Michiel [1 ,2 ,8 ]
机构
[1] Top Inst Food & Nutr, Wageningen, Netherlands
[2] Wageningen Univ, Microbiol Lab, Wageningen, Netherlands
[3] Univ Med Ctr, Div Gastroenterol & Nutr, Dept Pediat, Erasmus Med Ctr, Rotterdam, Netherlands
[4] Wageningen Univ, Nutr Metab & Genom Grp, Div Human Nutr, Wageningen, Netherlands
[5] INRA, UMR1319, Jouy En Josas, France
[6] Wageningen Univ, Dept Anim Sci, Wageningen, Netherlands
[7] Wilhelmina Childrens Hosp, Univ Med Ctr Utrecht, Dept Pediat Gastroenterol, Utrecht, Netherlands
[8] NIZO Food Res, Dept Hlth, Ede, Netherlands
关键词
INFLAMMATORY-BOWEL-DISEASE; T-CELL DEVELOPMENT; EXPRESSION; RESPONSES; MECHANISMS; RECEPTORS; INDUCTION; BACTERIA; DEFENSE; MUCINS;
D O I
10.1038/mi.2012.32
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
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.
引用
收藏
页码:567 / 579
页数:13
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