Infection of infants with human herpesvirus type 6 may be associated with reduced allergic sensitization and T-helper type 2 development

Background Epidemiological studies point to an inverse relationship between microbial exposure and the prevalence of allergic diseases. The underlying mechanism for this observation remains largely unknown, as well as the nature of the microbes involved. Objective To investigate the effects of early infection with human herpesviruses (HHVs) on IgE formation and T-helper type 2 (Th2) development in infants. Methods Serum was collected from children aged 18 months and assessed for IgE to common allergens and IgG to five common herpesviruses. Cord blood plasmacytoid dendritic cells (pDC) were exposed to HHV type 6 in vitro and mixed with allogeneic cord blood CD4(+) T cells. Cytokine levels were determined by ELISA and by flow cytometry. Results We found that children seropositive at 18 months of age to HHV type 6 were significantly less often IgE sensitized than seronegative children [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.009-0.68]. HHV type 6 also decreased the production of the Th2-associated cytokines IL-5 and IL-13 by CD4(+) T cells when co-cultured with allogeneic cord blood pDC. This was associated with an increased production of IFN-alpha by pDC exposed to HHV type 6. Conclusion These data indicate that an early childhood infection with HHV type 6 could down-regulate Th2 responses and reduce IgE formation to common allergens in a young child.