GM-CSF-deficient mice are susceptible to pulmonary group B Streptococcal infection

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-targeted mic e (GM(-/-)) cleared group B streptococcus (GBS) from the lungs more slowly than wild-type mice. Expression of GM-CSF in the respiratory epithelium of GM(-/-) mice improved bacterial clearance to levels greater than that in wi ldtype GM(+/+) mice. Acute aerosolization of GM-CSF to GM(+/+) mice signifi cantly enhanced clearance of GBS at 24 hours. GBS infection was associated with increased neutrophilic infiltration in lungs of GM(-/-) mice, while ma crophage infiltrates predominated in wild-type mice, suggesting an abnormal ity in macrophage clearance of bacteria in the absence of GM-CSF. While pha gocytosis of GBS was unaltered, production of superoxide radicals and hydro gen peroxide was markedly deficient in macrophages from GM(-/-) mice. Lipid peroxidation, assessed by measuring the isoprostane 8-iso-PGF(2 alpha), wa s decreased in the lungs of GM(-/-) mice. GM-CSF plays an important role in GBS clearance itt vivo, mediated in part by its role in enhancing superoxi de and hydrogen peroxide production and bacterial killing by alveolar macro phages.