Hotchkiss Brain Institute and Snyder Institute of Infection, Immunity and Inflammation, Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Health Sciences Centre, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada.
Integr Comp Biol. 2009 Sep;49(3):237-45. doi: 10.1093/icb/icp025. Epub 2009 Jun 10.
A host's defensive response to a pathogen is a phylogenetically ancient reaction that consists of a CNS-mediated series of autonomic, hormonal and behavioral responses that combine to combat infection. The absence of such defense results in greater morbidity and mortality and thus, these responses are essential for survival. The postnatal period represents a malleable phase in which the long-term behavior and physiology of the developing organism, including its immune responses, can be influenced. Postnatal challenge of the immune system by introduction of live replicating infections, or administration of bacterial and viral mimetics, can result in a multidomain alteration to the defenses of the adult host. Findings from our laboratory and others' indicate that the postnatal administration of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (PolyI:C), which mimic bacterial and viral infections respectively, can influence the neuroimmune response (generation of fever and production of cytokines) to a second challenge to the immune system in adulthood. This long-lasting alteration in the innate immune response is associated with myriad other effects on the animal's physiology and appears to be primarily mediated by a sensitized hypothalamic-pituitary-adrenal axis. Thus, a transient immunological perturbation to a developing animal may program the organism for subsequent health complications as an adult. In this review we discuss some of the potential mechanisms for these phenomena.
宿主对病原体的防御反应是一种进化古老的反应，它由中枢神经系统介导的一系列自主、激素和行为反应组成，共同抵抗感染。缺乏这种防御反应会导致更高的发病率和死亡率，因此，这些反应对生存至关重要。出生后时期是一个可塑性阶段，在此期间，发育中的生物体的长期行为和生理学，包括其免疫反应，可以受到影响。通过引入活的复制感染或给予细菌和病毒模拟物来挑战免疫系统的出生后，可以导致成年宿主防御系统的多领域改变。我们实验室和其他实验室的研究结果表明，出生后给予脂多糖（LPS）或聚肌苷酸：聚胞苷酸（PolyI:C），分别模拟细菌和病毒感染，可以影响成年后对免疫系统的第二次挑战的神经免疫反应（发热和细胞因子产生）。这种先天免疫反应的持久改变与动物生理学的许多其他影响有关，似乎主要是通过敏感的下丘脑-垂体-肾上腺轴介导的。因此，对发育中的动物进行短暂的免疫干扰可能会使机体在成年后出现随后的健康并发症。在这篇综述中，我们讨论了这些现象的一些潜在机制。
