Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
Institute of Medical Microbiology, RWTH University Hospital, Aachen, Germany.
FEBS J. 2022 Aug;289(16):4731-4757. doi: 10.1111/febs.16047. Epub 2021 Jun 19.
Education of our intestinal immune system early in life strongly influences adult health. This education strongly relies on series of events that must occur in well-defined time windows. From initial colonization by maternal-derived microbiota during delivery to dietary changes from mother's milk to solid foods at weaning, these early-life events have indeed long-standing consequences on our immunity, facilitating tolerance to environmental exposures or, on the contrary, increasing the risk of developing noncommunicable diseases such as allergies, asthma, obesity, and inflammatory bowel diseases. In this review, we provide an outline of the recent advances in our understanding of these events and how they are mechanistically related to intestinal immunity development and education. First, we review the susceptibility of neonates to infections and inflammatory diseases, related to their immune system and microbiota changes. Then, we highlight the maternal factors involved in protection and education of the mucosal immune system of the offspring, the role of the microbiota, and the nature of neonatal immune system until weaning. We also present how the development of some immune responses is intertwined in temporal and spatial windows of opportunity. Finally, we discuss pending questions regarding the neonate particular immune status and the activation of the intestinal immune system at weaning.
生命早期对肠道免疫系统的教育强烈影响着成年后的健康。这种教育强烈依赖于一系列必须在明确的时间窗口内发生的事件。从分娩时母体来源的微生物群初始定植,到从母乳喂养到断奶时的固体食物的饮食变化,这些早期生活事件确实对我们的免疫力产生了持久的影响,促进了对环境暴露的耐受,或者相反,增加了患非传染性疾病的风险,如过敏、哮喘、肥胖和炎症性肠病。在这篇综述中,我们概述了我们对这些事件的理解的最新进展,以及它们如何与肠道免疫发育和教育在机制上相关。首先,我们回顾了新生儿易患感染和炎症性疾病的情况,这与他们的免疫系统和微生物群变化有关。然后,我们强调了母体因素在保护和教育后代粘膜免疫系统中的作用,微生物群的作用,以及新生儿免疫系统的性质,直到断奶。我们还介绍了一些免疫反应是如何在时空机会窗口中交织在一起的。最后,我们讨论了关于新生儿特殊免疫状态和肠道免疫系统在断奶时激活的悬而未决的问题。