The effects of the route of viral infection on the balance of T helper immune responses.

The majority of pathogens enter the host through mucosal surfaces. Therefore, it stands to reason that production of protective mucosal immunity is a desirable outcome following vaccination for those infections. However, only a few mucosal vaccines have been developed to date, in part because of a general lack of understanding of mucosal immunity. The research presented in this dissertation is focused on the comparison of mucosal and systemic immunizations as a means of contributing to the understanding of how mucosal immune responses are induced. There is evidence that mucosal immunization can skew the balance of T helper (Th) 1 and Th2 immune responses; however, a clear picture of the effect of the route of infection on the balance of Th1 and Th2 responses has not been determined. In mice of the H-2d haplotype, oral (OR) reovirus infections elicit Th1-type immune responses while subcutaneous (SC) reovirus infections elicit both Th1- and Th2-type immune responses. Studies confirmed that IL-4 plays a major role in mediating the route of infection-dependent differences. However, mechanisms responsible for inducing the IL-4 differences were not clear. Therefore, we examined dendritic cells (DCs), which initiate primary immune responses and regulate the differentiation of naive Th cells into effector Th1 or Th2 cells, as a potential mechanism for inducing the route of infection-dependent differences. SC reovirus infections result in an increase in CD11b+ and CD8α+ DCs in the draining lymph nodes, with reovirus RNA being detected within the CD11b + DCs. In contrast, OR reovirus infection does not alter the phenotype of Peyer\u27s patch or mesenteric lymph node DC subpopulations; however, reovirus RNA was detectable in the CD11b+ DC subpopulation. Differences in IL-10 mRNA expression levels in DC subpopulations following SC and OR infections could partially contribute to the induction of characteristic Th immune responses. Overall, we have determined that DC subpopulations are affected by the route of infection, which likely translates into the differences observed in the induction of the Th1 and Th2 immune responses