Allergic lung inflammation enhances survival from pneumococcal pneumonia in mice

Pneumonia is estimated to be the second greatest disease burden worldwide and is the leading cause of infection-related death in the United States. S. pneumoniae remains the main cause of community acquired pneumonia (CAP), and mortality rates following pneumococcal infection are known to be elevated in individuals with well documented risk factors such as advanced age or underlying medical conditions like HIV and diabetes. The effectiveness of vaccination for at risk populations is complicated by the large number of known pneumococcal serotypes which emphasizes the need for further knowledge regarding the immunological response to infections in high-risk populations. Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia.;The purpose of this work was to clarify the effects of asthma on the subsequent susceptibility to invasive pneumococcal infection. Ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3 S. pneumoniae. Surprisingly, mice with ALI were significantly more resistant to lethal infection compared to non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of TGF-beta1. Neutrophil depletion prior to infection had no effect on the enhanced early clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytising bacteria, neutralization of IL-5 to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronate-sensitive, phagocytic SiglecFLOW alveolar macrophages within the airways following ALI.;Overall, these findings suggest that while the risk of developing IPD is increased in individuals with asthma, the resulting immune response to pulmonary pneumococcal infections may in fact be enhanced in patients with acute allergic inflammation, resulting in fewer complications and improved survival.