Effects of repeated respiratory syncytial virus infections on pulmonary dendritic cells in a murine model of allergic asthma.

BACKGROUND: Primary and secondary respiratory syncytial virus (RSV) infection differentially regulates preexisting allergic airway inflammation. OBJECTIVES: The present study was designed to determine the effects of primary and secondary low-grade RSV infections on pulmonary dendritic cell (DC) functions. METHODS: Eight groups of BALB/c mice were used: one group each for control primary and secondary sensitization, primary and secondary sensitization to Dermatophagoides farinae (Derf) allergen, primary and secondary infection with RSV, and primary and secondary sensitization to Derf plus infection with RSV. CD11c+ pulmonary DCs were isolated from these mice and then transferred to naïve mice followed by intranasal Derf challenge. Furthermore, either anti-IL-12 monoclonal antibody (alphaIL-12 mAb) or anti-IL-10 (alphaIL-10) mAb were injected into donor mice after Derf challenge and during RSV infection to determine the involvement of IL-12 and IL-10. RESULTS: Primary RSV infection failed to induce polarization in DCs since it failed to induce IL-10 and IL-12 production in Derf-sensitized donor lung. In contrast, secondary RSV infection significantly enhanced IL-12 production from Derf-sensitized donor lung, thereby enhancing both Th1 and Th2 responses. During RSV infection, alphaIL-12 but not alphaIL-10 mAb treatment blocked these immunological effects. CONCLUSION: Via IL-12, DCs may play a critical role in shifting the immune response in this experimental model of repeated respiratory viral infection in allergic asthma