Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice
Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice
复制标题
DOI：
10.1038/mi.2012.32
复制
发表时间：
2012-09-01
影响因子：
8
通讯作者：
Kleerebezem, Michiel
中科院分区：
文献类型：
--
作者：
El Aidy, Sahar;van Baarlen, Peter;Kleerebezem, Michiel
在无菌小鼠与其常规出生和抚养的同胞（常规化）的总粪便微生物群落定殖期间，肠粘膜免疫系统启动并维持平衡的免疫应答。然而，这些对微生物群的平衡、适当反应的遗传调节是模糊的。在此，无菌和常规化小鼠的组合分析显示，可以检测到在常规化后第4天开始的主要分子应答，强烈诱导先天免疫功能，随后刺激适应性免疫应答以及在常规化的后期阶段适应性免疫细胞的发育和扩增。这项研究全面概述了由肠道微生物群共同介导的小鼠发育和免疫相关的细胞途径和过程，并提出了参与这种重编程的机制。动态的，区域依赖性的粘膜反应的殖民微生物群揭示了潜在的转录签名控制肠道稳态在健康小鼠，这可能有助于破译人类肠道炎症性疾病的通路失调的遗传基础。
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.