Pathological Examination of Lung Tissues in Influenza A Virus-Infected Mice

Abstract

SUMMARY:This study examined pathological changes in the lung tissues of young and aged mice infected with influenza virus. Young mice inoculated with influenza virus showed body weight loss at 4 days post-infection (dpi), meanwhile body weight decrease started from 9 dpi in the aged mice. We histopathologically examined the lungs of these mice. Immunohistochemical examination revealed that viral antigen-positive bronchiolar and alveolar epithelial cell numbers at 3 dpi were significantly higher in young mice than in the aged ones. Further, viral antigen-positive cells were observed at 9 dpi in the aged mice, but not in the young ones. Diffuse and severe bronchointerstitial pneumonia characterized by the accumulation of polymorphonuclear leukocytes (PMNs) was observed in young mice at 6 dpi. Histopathological changes in the aged mice were milder than those in the young mice. Moreover, T cell and macrophage accumulation in the lungs was significantly higher in the young mice than in the aged mice at 9 dpi. These results suggest that there may be a correlation between the relatively low level of infiltration of PMNs, macrophages, and T lymphocytes and the delayed body weight loss and longer lasting infections observed in the lungs of the aged mice. These findings provide detailed insights into the age-specific course of infection in young and aged populations with associated differences in lung pathology.

Impaired heterologous immunity in aged ferrets during sequential influenza A H1N1 infection

“…Here we found that aged ferrets did not recover to their original weight following sequential heterologous H1N1 influenza infection (Figure 4), a finding consistent with observations of long-term disability in the elderly following repeated influenza exposure (McElhaney, 2005). Clinical signs in our aged ferret model were also in agreement with previous animal studies where the disease severity of aged animal was modestly increased during 1° infection (Guo et al, 2012; Josset et al, 2012; Muto et al, 2012; Pica et al, 2012) but importantly, heterologous monosubtypic 1° infection – 2° challenge caused severe morbidity in aged ferrets similar to previous rechallenge mouse studies (Bender and Small, 1993; Decman et al, 2010). Our work together with previously published studies has begun to suggest a profile of the aged clinical following subsequent influenza infection.…”

“…Age-related immune dysregulation modestly impacts disease severity in animal models of primary influenza infection (Guo et al, 2012; Josset et al, 2012; Muto et al, 2012; Pica et al, 2012). Heterosubtypic influenza A immune memory is severely impaired in aged animals (Bender and Small, 1993; Decman et al, 2010), although the elderly's sensitivity to monosubtypic antigenic change is unclear.…”

Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development

“…was observed following a second heterologous infection in ferrets, which allowed the development of significant morbidity (12). These findings are in agreement with other studies focusing on aged animals, which showed that the clinical severity of primary infection is only moderately accentuated (13)(14)(15)(16), while heterologous secondary infection induced severe disease (12,17,18). The induction of influenza virus-specific memory T cells is extensively investigated as they are responsible for heterologous protection in secondary natural infections with another influenza strain [reviewed in (19)].…”