Decreased pulmonary clearance of S. pneumoniae following influenza A infection in mice

Abstract

In children, the incidence of complicated pneumonias (including empyemas and lung abscesses) associated with Streptococcus pneumoniae infection has increased in recent years. In many cases, these complicated pneumonias followed flu-like illnesses. To determine mechanisms behind this association, a murine model of sequential pulmonary infection has been developed. BALB/cJ mice infected with influenza A had mild pulmonary inflammation that resolved within 5–7 days. Seven days following their initial ‘treatment’ (mock infection or influenza exposure), mice were challenged with 10 6 cfu of S. pneumoniae, and their lungs were harvested at intervals for analysis. Lungs of influenza-exposed mice demonstrated greater colony counts 24 and 48 h following S. pneumoniae exposure compared to control mice. In addition, neutrophil numbers were significantly increased in the influenza/ S. pneumoniae sequentially-infected animals compared to S. pneumoniae infection alone (1.4±0.6×10 6 vs. 0.06±0.07×10 6 cells, P<0.05, 24 h). Influenza-exposed animals had greater levels of IL-1β and TNF-α in lung homogenates following S. pneumoniae inoculation. These data demonstrate that mice exposed to influenza have enhanced inflammatory responses and increased bacterial burden following S. pneumoniae exposure than do control mice. This model will be useful in defining mechanisms behind the enhanced susceptibility to S. pneumoniae that occurs after influenza exposure.