Neuroendocrine Modulation of Neonatal Antiviral Immunity

新生儿是一个免疫缺陷的宿主，它对出生时或出生后不久可能遇到的病原体产生免疫反应的能力严重受损。因此，新生儿在很大程度上依赖于母体来源的免疫，这种免疫在产前通过经胎盘途径在产后通过初乳和母乳获得，以保护他们在出生后的几周内免受各种感染。本应用程序的主要目的是确定产妇心理应激及其相关的神经内分泌源性肽和激素的产生对新生儿免疫力和对传染病的易感性的影响。提出这项研究的基本原理是基于这样一个事实，即在成年人中，有大量证据表明心理压力通过各种神经内分泌相关机制显著影响免疫功能。然而，尽管神经内分泌-免疫相互作用在成人中明显存在，但关于这种相互作用在新生儿和幼儿中所起的作用，特别是这种相互作用如何影响免疫介导的对病原体的防御，目前还缺乏知识。本提案中描述的研究将使用一个完善的单纯疱疹病毒（HSV）感染小鼠模型来验证以下假设：产前和产后母体应激（急性和慢性），以及与应激相关的母体下丘脑-垂体-肾上腺（HPA）轴的激活改变了母体源抗体向新生儿的转移，以及新生儿和幼龄婴儿所暴露的母体皮质酮水平。预计这两个因素将反过来影响新生儿母体源性免疫的可得性和利用以及幼龄婴儿单纯疱疹病毒特异性免疫的产生。这些参数对新生儿HSV感染发病机制的影响也将被确定。总的来说，这些研究将确定产妇压力对新生儿对HSV易感性的影响，以及对其他免疫抵抗并对新生儿健康构成威胁的病原体易感性的潜在影响。这类研究可以推动就压力管理和建立社会支持网络等问题提供产妇咨询的努力，以此作为提高新生儿免疫力的手段。

The neonate is an immunodeficient host that is severely compromised in its ability to generate an immune response to pathogens which may be encountered at, or shortly after birth. Thus, neonates rely heavily on maternally-derived immunity, obtained both prenatally via transplacental means postnatally via the colostrums and breast milk, to protect them from a variety of infections during the first few weeks of like. The broad objective of this application is to determine the impact of maternal psychological stress and its associated production of neuroendocrine-derived peptides and hormones on neonatal immunity and susceptibility to infectious disease. The rationale for the proposed research is based on the fact that, in the adult, there is substantial evidence that psychological stress significantly affects immune function via a variety of neuroendocrine-associated mechanisms. However, despite the clear existence of neuroendocrine- immune interactions in adults, there is a dearth of knowledge as to the role that such interactions play in the neonate and young infant and, in particular, how such interactions affect immune-mediated defense against pathogens. The studies described in this proposal will use a well-established murine model of herpes simplex virus (HSV) infection to test the hypothesis that pre- and postnatal maternal stress (both acute and chronic), and stress-associated activation of the maternal hypothalamic- pituitary adrenal (HPA) axis alters both the transfer of maternally-derived antibody to the neonate and the levels of maternal corticosterone to which the neonate and young infant are exposed. It is expected that both of these factors will, in turn, affect both the availability and utilization of maternal-derived immunity in the neonate and the generation of HSV-specific immunity in the young infant. The effects of each of these parameters on the pathogenesis of neonate HSV infection will also be determined. Overall, these studies will determine the impact of maternal stress on neonatal susceptibility to not only HSV but also its potential impact on susceptibility to other pathogens that are immunologically resisted and pose a threat to neonatal health. Such studies may serve as the impetus for efforts to provide maternal counseling on issues such as stress management and the establishment of social support networks as a means to enhance neonatal immunity.