Pulmonary and Systemic Host Response toStreptococcus pneumoniaeandKlebsiella pneumoniaeBacteremia in Normal and Immunosuppressed Mice

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Abstract
Mortality related to bacteremic pneumonia remains high, and the role of sepsis in inflammation, pulmonary injury, and death remains unclear, mostly in leukopenic states. In the present study, the microbiology, histopathology, and host response toStreptococcus pneumoniaeandKlebsiella pneumoniaeinfection were determined in an experimental model of bacteremia in immunocompetent and leukopenic mice. Leukocyte depletion by cyclophosphamide did not impair the early clearance of pneumococci from blood but facilitated growth in lungs. By contrast, klebsiellae rapidly grew in blood of leukopenic mice. These observations suggest that tissue-based phagocytes and circulating leukocytes, respectively, play prominent roles inS. pneumoniaeandK. pneumoniaeeradication. The kinetics of leukocyte recruitment in lungs duringS. pneumoniaebacteremia suggested early strong inflammation in immunocompetent mice that is associated with tumor necrosis factor alpha release and histological disorders, including cell debris and surfactant in alveolar spaces. Leukocyte depletion further stimulated pulmonary capillary leakage both inS. pneumoniaeandK. pneumoniaebacteremia, which seemed attributable to bacterial virulence factors. Nitric oxide production did not differ significantly among groups. Leukopenia and low platelet counts characterized the late stage of bacteremia for both strains, but onlyK. pneumoniaealtered renal function. Understanding the pathogenesis of bacteremia will help establish beneficial therapies for both sepsis and pneumonia.