The innate and adaptive immune response to Pneumonia Virus of Mice in a resistant and a susceptible mouse strain

Respiratory syncytial virus (RSV) is the leading cause of infant bronchiolitis, but the mechanisms underlying host susceptibility to severe infection are still largely unknown. The closely related pneumonia virus of mice (PVM) causes a similar immune-mediated disease in rodents, which makes possible the analysis of host factors that lead to severe illness in mice. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in the Balb/c mouse strain with those of the more resistant C57Bl/6 strain. The two strains often show opposite T-helper responses, with C57Bl/6 mice having a greater bias towards Th1 responses and Balb/c mice towards Th2 responses. Based on studies of PVM and RSV in mice, we expected the greater susceptibility of Balb/c mice to PVM 15 infection to be associated with enhanced proinflammatory chemokines, Th2-biased cytokines, and eosinophilic disease. We found that the two strains have Th1-biased responses to PVM infection in both the innate and adaptive arms of the immune response. Eosinophilia did not develop in either strain upon infection with PVM 15. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Neutrophils were more predominant in infected Balb/c lungs than in C57Bl/6 mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses, and clearance appeared to be mediated by lymphocytes rather than neutrophils. PVM-specific IFN-γ production by splenocytes in C57Bl/6 mice was stronger earlier and weaker at late time points after a sublethal infection than that of Balb/c mice. Additionally, the antibodies produced in the blood and in the lungs of sublethally infected C57Bl/6 mice reached an earlier peak and were more capable of neutralizing PVM in vitro than that of Balb/c mice, despite similar IgG titres and lower mucosal IgA titres in C57Bl/6 mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM