Modulation of the immune response mediated by oral transgene administration of IL-10

In the current study, we analyze the immunomodulatory effect of oral transgene administration of IL-10 using a mice model of viral inflammation. Salmonella harboring a plasmid encoding the IL-10 gene (SLIL10) was administered by the oral route together with Salmonella carrying a plasmid encoding the glycoprotein D or B (SLgD, SLgB) of Herpes simplex virus type 2 (HSV-2). This resulted in a high inhibition of the cellular and human immune response against the viral proteins. When mice immunized against the HSV proteins were challenged with 10 lethal doses of HSV-2 by the intravaginal route, only those that had also received SLIL10 showed severe lesions and died. When Salmonella harboring pIL10 was administered orally to mice immunized by the intramuscular route with a plasmid encoding gD, inhibition of cellular and humoral immune responses were also observed but to a lesser extent than with oral immunization. By means of adoptive transfer experiments and in vitro experiments, we have subsequently determined that the mechanism possibly involved in the inhibition of the immune response could be a reduced antigenic presentation when mice receive SLIL10 that induced a state of anergy on specific T lymphocytes.