Role of IL-12b in the regulation of viral pathogenesis in the respiratory tract (67.15)

Abstract

Abstract Human metapneumovirus (hMPV), a newly-recognized member of the Paramyxoviridae family, mediate serious lower respiratory tract illness in very young children, the elderly and immunocompromised patients. The mechanisms that regulate the host immune response to hMPV are largely unknown. IL-12b is an important mediator in limiting lung inflammation and Th2 responses. However, the relative contributions of IL-12b to viral pathogenesis have not been extensively studied. We have observed that hMPV infection induces a robust and sustained production of IL-12b in the lung of infected mice beyond the resolution phase, suggesting that this cytokine plays an important role in hMPV infection. Using an IL-12b deficient (IL-12 KO) mouse model of infection we determined the role of IL-12b in hMPV pathogenesis. Our data indicate that the absence of IL-12b increased the disease severity in the course of hMPV infection as indicated by a significant increase in body weight loss (>20%) in deficient mice when compared to WT animals. In addition, a three-fold increase in airway resistance, measured in artificially ventilated conditions by the Flexivent system was observed in the IL-12b KO mice. Furthermore, relative to WT mice, an altered CD4+ and CD8+ T cell responses in lung and draining lymph nodes was observed in hMPV-infected IL-12b KO mice. In conclusion, these findings indicate that IL-12b plays a regulatory role in disease pathogenesis and immune responses in the course of hMPV infection.