Transplacental transfer and subsequent neonate utilization of herpes simplex virus-specific immunity are resilient to acute maternal stress

Abstract

Neonates are severely compromised in the ability to generate an immune response to pathogens and thus rely heavily on maternally derived immunity that is acquired by transplacental and transmammary means. The passive transfer of maternal herpes simplex virus (HSV)-specific antibody is critical in determining the outcome of neonatal HSV infection. In adults, psychological stress alters immune responsiveness via the increased level of corticosterone that is produced as a result of hypothalamic-pituitary-adrenal axis activation. Although the behavioral and neuroendocrine effects of pre- and postnatal stress-induced increases in corticosterone are well documented, the effects of maternal stress on the efficacy of prenatally transferred and neonatally developed viral immunity has yet to be addressed. By using a well-established prenatal restraint-and-light stress mouse model, we investigated the effects of increased maternal corticosterone on the passive transfer of total and HSV-specific immunoglobulin G (IgG) antibody and subsequent neonatal susceptibility to HSV infection. Serum corticosterone levels in pregnant mice were significantly increased in response to restraint-and-light stress, and fetuses derived from these stressed mice had significantly elevated levels of corticosterone. Despite the increases in corticosterone, the passive transfer of total and HSV-specific IgG antibody persisted and, in turn, protected the neonate from systemic viral spread. Therefore, prenatal stress did not increase the susceptibility of neonates to HSV type 2-associated mortality. These findings demonstrate the resiliency of the passive transfer of protective HSV-specific immunity under conditions of acute psychological stress.

FIG. 1.

Maternal immunization with HSV-2 protects progeny from HSV-2-induced mortality in a dose-dependent manner. Female mice 7 to 8 weeks of age were immunized s.c. in both of the rear footpads with HSV-2 three times at 1-week intervals. Two-day-old mice born to these HSV-immune mothers were infected i.p. with 1 × 10², 5 × 10², 1 × 10³, or 5 × 10³ PFU of HSV-2 in a volume of 20 μl. Neonates born to nonimmunized mothers were infected i.p. with 10² PFU of HSV-2. Neonatal mice were monitored daily for mortality until 15 days postinfection.

FIG. 2.

Passive transfer of total and HSV-specific IgG is preserved in the presence of prenatal stress. Female mice 7 to 8 weeks of age were immunized s.c. in both of the rear footpads with HSV-2 three times at 1-week intervals. A subset of these HSV-immune mice was subjected to restraint-and-light stress on days 12 to 17 postcoitus. Serum was obtained from both the neonates and the mothers immediately following birth and analyzed for total IgG (A) and HSV-specific IgG (B) by ELISA. Values represent the mean ± the standard error of the mean.

FIG. 3.

Prenatal restraint-and-light stress does not affect the susceptibility of neonatal mice to HSV infection. Female mice 7 to 8 weeks of age were immunized s.c. in both of the rear footpads with HSV-2 three times at 1-week intervals. A subset of these HSV-immune mice was subjected to restraint-and-light stress on days 12 to 17 postcoitus. A subset of neonates remained with their HSV-immune, prenatally stressed or nonstressed mothers or with their nonimmunized mothers (A). A second subset of mice born to HSV-immune, prenatally stressed and nonstressed mice was fostered to nonimmunized mice (B). All neonates were infected i.p. at 2 days of age with 10² PFU of HSV-2 in a volume of 20 μl. Neonatal mice were monitored daily for mortality until 20 days postinfection.