Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor

• Published in: Nature (London) Vol. 351; no. 6322; pp. 155 - 158
• Main Authors: Ezekowitz, R. A. B, Williams, D. J, Koziel, H, Armstrong, M. Y. K, Warner, A, Richards, F. F, Rose, R. M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 09.05.1991; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Cell Line; Cells, Cultured; Cellular biology; Cloning, Molecular; Fluorescein-5-isothiocyanate; Fluoresceins; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; Humans; Immunity (Disease); Lectins, C-Type; Life cycle. Host-agent relationship. Pathogenesis; Macrophages - metabolism; Macrophages - microbiology; Macrophages - ultrastructure; Male; Mannans; mannose; Mannose-Binding Lectins; Medical research; Oxygen - metabolism; Parasites; Phagocytosis; Pneumocystis - metabolism; Pneumocystis carinii; Protozoa; Pulmonary Alveoli - immunology; Pulmonary Alveoli - microbiology; Rats; Rats, Inbred Strains; Receptors, Cell Surface; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Thiocyanates; Transfection; Protozoa; Rat; Rodentia; Molecular interaction; Pneumocystis carinii; Mannose; Electron microscopy; Uptake; Defense; Mechanism; Vertebrata; Membrane receptor; Mammalia; Sporozoa; Macrophage
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/351155a0

Human exposure to Pneumocystis carinii is common but, in the absence of acquired or genetic dysfunction of either cellular or humoral immunity, exposure rarely leads to illness. Although alveolar macrophages can degrade P. carinii, macrophage receptors involved in P. carinii recognition have not been clearly defined. Characterization of a predominant surface glycoprotein of the high mannose type led us to investigate the role of the macrophage mannose receptor in this process. We report here that binding and uptake of cultured rat P. carinii by human and rat alveolar macrophages is reduced by 90% in the presence of competitive inhibitors of mannose receptor activity and by adherence of alveolar macrophages to mannan-coated surfaces. Further, only those COS cells transfected with the human macrophage mannose receptor complementary DNA that express surface mannose receptors bind and ingest P. carinii. These studies establish that the macrophage mannose receptor is sufficient for uptake of P. carinii and emphasize the role of the alveolar macrophage in first-line host defence against P. carinii.