The relative contribution of resident pulmonary alveolar macrophage and inflammatory polymorphonuclear neutrophils in host resistance to pulmonary infection by Candida albicans.
Cortisone (CA) or cyclophosphamide (Cy) treatment of mice was used to investigate the relative contributions of pulmonary alveolar macrophages (PAM) and inflammatory neutrophils (PMN) in the initial defense against intratracheal challenge (IT) with Candida albicans. Mice treated with either CA or Cy were susceptible to IT challenge with 10-100 x less C. albicans than were untreated mice. Untreated mice rapidly eliminated C. albicans from their lungs with the majority of the organisms being cleared within three hours of challenge. Mice treated with CA initially cleared some of the C. albicans but were unable to clear all the C. albicans as did the untreated mice. Mice treated with Cy were unable to clear C. albicans from their lungs. Candida albicans did not disseminate from the lungs of untreated mice, while in both of the treated groups, C. albicans disseminated to the liver, spleen, brain and kidneys, rapidly killing the treated hosts. Analysis of the changes in cells in lung lavage fluids collected at various times after C. albicans challenge, revealed that large numbers of PMN accumulated in the lungs of both untreated and CA-treated mice, whereas PMN were virtually undetectable in lavage fluids from Cy-treated mice. Resident PAM from untreated mice were able to kill approximately 70% of 10(5) C. albicans in a 3 hr in vitro killing assay. By contrast, at similar effector:target ratios, resident PAM from Cy-treated mice killed only about 20% of the inoculum and resident PAM from CA-treated mice were unable to kill C. albicans. PMNs from both untreated and CA-treated mice killed approximately 70% of 10(5) C. albicans in vitro. The data indicates that both PAM and PMN were critical to the initial clearance of C. albicans from pulmonary tissue. The accumulation of PMN in the lungs appeared to be required for the complete clearance of C. albicans from the lungs yet was not sufficient to inhibit dissemination of C. albicans from the lungs in CA-treated mice. The presence of PAM with in vitro candidacidal abilities appeared to be required for both the clearance of C. albicans and inhibition of dissemination of C. albicans from the lungs. Compromise of either PAM or PMN function can lead to increased pulmonary susceptibility to C. albicans.
Sawyer
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RT
Trudeau Institute, Inc., Saranac Lake, NY 12983.
Harmsen
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AG
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D002177:Candidiasis / Q000188:drug therapy / Q000276:immunology*; D002470:Cell Survival; D015169:Colony Count, Microbial; D003348:Cortisone / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*
D003520:Cyclophosphamide; D003348:Cortisone