The response of aged mice to primary infection and re-infection with pneumonia virus of mice depends on their genetic background

摘要

The pneumonia virus of mice (PVM) model is used to study respiratory syncytial virus (RSV) pathogenesis. The outcome of PVM infection varies in different inbred mouse strains, BALB/c being highly susceptible and C57BL/6 more resistant. As the disease symptoms induced by RSV infection can become more severe as people age, we examined the primary and secondary immune responses to infection with PVM in aged BALB/c and C57BL/6 mice. Based on clinical parameters, aged C57BL/6 mice displayed less severe disease than young adult mice when infected with 3000 pfu of PVM-15, while BALB/c mice were equally susceptible at both ages showing significant weight loss and high levels of virus replication. Furthermore, after primary infection the CD4(+) T cell numbers in the lungs were higher in young adult mice, while the CD8(+) T cell numbers were comparable in both age groups and strains. When either C57BL/6 or BALB/c mice were infected with PVM as young adults and then re-infected as aged mice, they were protected from clinical disease, while virus replication was reduced. In contrast to mice with a primary PVM-infection, re-infected mice did not have infiltration of neutrophils or inflammatory mediators in the lung. BALB/c mice had higher virus neutralizing antibody levels in the serum and lung than C57BL/6 mice upon reinfection. Re-infection with PVM led to significant influx of effector CD4(+) T cells into the lungs when compared to aged mice with a primary infection, while this cell population was decreased in the lung draining lymph nodes in both mouse strains. After re-infection the effector CD8(+) T cell population was also decreased in the lung draining lymph nodes in both mouse strain when compared to aged mice after primary infection. However, the central memory CD4(+) and CD8(+) T cells were significantly enhanced in numbers in the lungs and draining lymph nodes of both mouse strains after re-infection, and these numbers were higher for C57BL/6 mice. (C) 2015 Elsevier GmbH. All rights reserved.