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Phagocytic activity and monocyte chemotactic protein expression by pulmonary macrophages in persistent pulmonary
Wu He1, Arturo Casadevall, Sunhee C Lee
1Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
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.
Insights
Pulmonary macrophages phagocytize Cryptococcus neoformans, producing monocyte chemotactic protein 1 (MCP-1). This process is influenced by infection duration, opsonins, and aging, highlighting macrophage regulation in persistent cryptococcosis.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Cryptococcus neoformans persistence in immunocompetent hosts remains poorly understood.
- Pulmonary macrophages (PuM) play a critical role in host defense against fungal infections.
- Monocyte chemotactic protein 1 (MCP-1) is a key chemokine involved in inflammatory responses.
Purpose of the Study:
- To investigate the phagocytic capacity of PuM for C. neoformans.
- To determine MCP-1 production by PuM during persistent infection.
- To elucidate the influence of infection duration, opsonins, and aging on these processes.
Main Methods:
- A rat model of persistent C. neoformans infection was utilized.
- Phagocytosis assays and MCP-1 production measurements were performed.
- Immunohistochemistry and ex vivo studies assessed MCP-1 localization and PuM function.
Main Results:
- Macrophage phagocytosis efficiency varied with infection time and opsonin type, influenced by CD11b/c and CD18 expression.
- Lung MCP-1 levels increased during infection, localized to macrophages and epithelioid cells.
- Antibody opsonization was more effective than serum for phagocytosis and MCP-1 induction; aging impaired MCP-1 production.
Conclusions:
- Macrophages are a significant source of MCP-1 during pulmonary cryptococcosis.
- MCP-1 production by PuM is actively regulated and stimulated by C. neoformans phagocytosis.
- Opsonin type and host aging significantly impact macrophage function and MCP-1 response in cryptococcosis.