Divisions of Veterinary Pathology, Infection and Immunity, School of Clinical Veterinary Science, University of Bristol, Langford House, Langford, UK.
Clin Exp Immunol. 2010 Jun;160(3):431-9. doi: 10.1111/j.1365-2249.2010.04090.x. Epub 2010 Feb 22.
Early-life exposure to appropriate microbial flora drives expansion and development of an efficient immune system. Aberrant development results in increased likelihood of allergic disease or increased susceptibility to infection. Thus, factors affecting microbial colonization may also affect the direction of immune responses in later life. There is a need for a manipulable animal model of environmental influences on the development of microbiota and the immune system during early life. We assessed the effects of rearing under low- (farm, sow) and high-hygiene (isolator, milk formula) conditions on intestinal microbiota and immune development in neonatal piglets, because they can be removed from the mother in the first 24 h for rearing under controlled conditions and, due to placental structure, neither antibody nor antigen is transferred in utero. Microbiota in both groups was similar between 2 and 5 days. However, by 12-28 days, piglets reared on the mother had more diverse flora than siblings reared in isolators. Dendritic cells accumulated in the intestinal mucosa in both groups, but more rapidly in isolator piglets. Importantly, the minority of 2-5-day-old farm piglets whose microbiota resembled that of an older (12-28-day-old) pig also accumulated dendritic cells earlier than the other farm-reared piglets. Consistent with dendritic cell control of T cell function, the effects on T cells occurred at later time-points, and mucosal T cells from high-hygiene, isolator pigs made less interleukin (IL)-4 while systemic T cells made more IL-2. Neonatal piglets may be a valuable model for studies of the effects of interaction between microbiota and immune development on allergy.
生命早期接触适当的微生物菌群会促进高效免疫系统的扩张和发育。异常发育会增加过敏疾病的可能性或增加感染的易感性。因此，影响微生物定殖的因素也可能影响生命后期免疫反应的方向。需要一种可操作的动物模型，以研究环境对生命早期微生物群和免疫系统发育的影响。我们评估了在低卫生条件（农场、母猪）和高卫生条件（隔离器、配方奶）下饲养对新生仔猪肠道微生物群和免疫发育的影响，因为它们可以在出生后 24 小时内从母亲身上取出，在受控条件下进行饲养，并且由于胎盘结构，胎内既不转移抗体也不转移抗原。两组仔猪的肠道菌群在 2 至 5 天之间相似。然而，到 12-28 天时，在隔离器中饲养的仔猪的菌群比在隔离器中饲养的仔猪的菌群更为多样化。两组仔猪的肠黏膜中均有树突状细胞积累，但在隔离器仔猪中积累速度更快。重要的是，少数 2-5 日龄的农场仔猪的菌群与较年长（12-28 日龄）仔猪的菌群相似，其树突状细胞的积累也早于其他在农场饲养的仔猪。与树突状细胞控制 T 细胞功能一致，对 T 细胞的影响发生在稍后的时间点，来自高卫生、隔离器仔猪的黏膜 T 细胞产生的白细胞介素（IL）-4 较少，而全身 T 细胞产生的 IL-2 较多。新生仔猪可能是研究微生物群与免疫发育相互作用对过敏影响的有价值模型。
