title: Phagocytic activity and monocyte chemotactic protein expression by pulmonary macrophages in persistent pulmonary cryptococcosis.
abstract: The mechanisms by which Cryptococcus neoformans persists in an immunocompetent host are not well understood. Using a rat model of persistent infection, we investigated the ability of pulmonary macrophages (PuM) to phagocytize C. neoformans and produce monocyte chemotactic protein 1 (MCP-1) as a function of the length of time of infection and opsonin. The ability of macrophages to affect serum-mediated phagocytosis varied over the course of infection and was dependent on CD11b/c and CD18 expression. Infection resulted in increased MCP-1 levels within the lung, though the actual amounts varied over the course of infection. Immunohistochemical studies localized MCP-1 expression to macrophages and epithelioid cells. Enhanced production of MCP-1 by PuM from infected rats was confirmed by ex vivo studies. Induction of MCP-1 following serum-mediated phagocytosis was observed for PuM from both infected and noninfected rats and depended on the interaction of C. neoformans with CD11b/c and CD18. Specific antibody was more efficient than serum in promoting phagocytosis and consistently elicited more MCP-1. The relative amount of MCP-1 produced in association with phagocytosis was similar for PuM at all lengths of time of infection. Decreased MCP-1 production was observed for PuM obtained from older rats, including long-term (8 to 10 months)-infected and age-matched controls, suggesting that aging may affect the production of MCP-1 by PuM in response to cryptococcal infection. In summary, our results show that macrophages are an important source of MCP-1 during pulmonary cryptococcosis and that MCP-1 production is actively regulated during infection. Furthermore, we find that phagocytosis of C. neoformans can serve as an important stimulus for MCP-1 production by PuM, though the efficiency of this process is dependent on the opsonin type and may be affected by aging.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: He
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.forename: Sunhee C
authors.initials: SC
authors.lastname: Lee
authors.forename: David L
authors.initials: DL
authors.lastname: Goldman
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism*; D002908:Chronic Disease; D003453:Cryptococcosis / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology*; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D008297:Male; D010587:Phagocytosis; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; D018932:Chemokine CCL2