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.
