Impact of primary influenza infection on the immune response to secondary bacterial infection in aged mice

Background: Increased susceptibility of older populations to secondary bacterial pneumonia-like infections following influenza infection has been well documented.¹ Recent evidence in mouse models suggests that this increased risk from secondary bacterial infection occurs through a desensitization of the innate immune response.² This recent finding, however, does not account for potential differences in immune responsiveness due to age.

Materials and methods: To address this parameter, we used three age groups (aged, adult, and young mice) to evaluate the role of age in influenza-mediated vulnerability to secondary bacterial challenge with Pseudomonas aeruginosa. All mice were evaluated for multiple parameters including: (i) survival; (ii) lung bacterial load; (iii) total lung protein content; (iv) immune cell infiltration; (v) cytokine/chemokine expression; and (vi) toll-like receptor (TLR) RNA expression profiles.

Results: Prior challenge with influenza contributed to aberrant cytokine/chemokine profiles and increased lung cellular infiltrate in response to secondary bacterial infection across all age groups, supporting a critical role for influenza infection in the alteration of immune responses to other pathogens. Also similar to human influenza, these changes were exacerbated by age in mice as demonstrated by increased bacterial load, mortality, and total lung protein content (an indicator of lung damage) after P. aeruginosa challenge.

Conclusions: These data support a potential role for virus-mediated and age-mediated alteration of innate immune effectors in the pathogenesis of influenza and the increased susceptibility of influenza virus infected mice to secondary bacterial infection. The understanding of the complex interaction of host and pathogen - and the role of age - in human influenza is critical in the development of novel therapeutics and improved vaccine approaches for influenza. Our results support further examination of influenza-mediated alterations in innate immune responses in aged and non-aged animals to allow elucidation of the molecular mechanisms of influenza pathogenesis in humans.