title: Exogenous heat-killed Escherichia coli improves alveolar macrophage activity and reduces Pneumocystis carinii lung burden in infant mice.
abstract: Pneumocystis carinii is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised individuals. Infants appear to be particularly susceptible to Pneumocystis pulmonary infections. We have previously demonstrated that there is approximately a 3-week delay in the clearance of Pneumocystis organisms from pup mouse lungs compared to that in adults. We have further shown that there is approximately a 1-week delay in alveolar macrophage activation in pups versus adult mice. Alveolar macrophages are the primary effector cells responsible for the killing and clearance of Pneumocystis, suggesting that pup alveolar macrophages may be involved in the delayed clearance of this organism. Alveolar macrophages cultured in vitro with Pneumocystis alone demonstrate little to no activation, as indicated by a lack of cytokine production. However, when cultured with lipopolysaccharide (LPS) or zymosan, cytokine production was markedly increased, suggesting that pup alveolar macrophages are specifically unresponsive to Pneumocystis organisms rather than being intrinsically unable to become activated. Furthermore, pup mice treated with aerosolized, heat-killed Escherichia coli in vivo were able to clear Pneumocystis more efficiently than were control mice. Together, these data suggest that while pup alveolar macrophages are unresponsive to P. carinii f. sp. muris organisms, they are capable of activation by heat-killed E. coli in vivo, as well as LPS and zymosan in vitro. The lack of response of pup mice to P. carinii f. sp. muris may reflect protective mechanisms specific to the developing pup lung, but ultimately it results in insufficient clearance of Pneumocystis organisms.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA.
authors.forename: Kerry M
authors.initials: KM
authors.lastname: Empey
authors.forename: Melissa
authors.initials: M
authors.lastname: Hollifield
authors.forename: Beth A
authors.initials: BA
authors.lastname: Garvy
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology*; D006358:Hot Temperature; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D008262:Macrophage Activation / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010587:Phagocytosis; D045363:Pneumocystis carinii / Q000302:isolation & purification*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000382:microbiology
chemical_list: D016207:Cytokines