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Macrophages from human immunodeficiency virus-positive persons are defective in host defense against Histoplasma
S Chaturvedi1, P Frame, S L Newman
1Department of Internal Medicine, University of Cincinnati College of Medicine, Ohio.
Abstract:
The phagocytic and fungistatic activity of monocyte-derived macrophages from human immunodeficiency virus (HIV)-positive persons against Histoplasma capsulatum yeasts was determined. Macrophages from HIV-positive patients were profoundly deficient in their capacity to recognize and bind H. capsulatum, but ingestion of bound yeasts was normal. The binding of H. capsulatum by patient macrophages tended to decrease with a decrease in CD4+ T lymphocyte counts. Another major defect was that patient macrophages were more permissive for the intracellular growth of H. capsulatum. Macrophages from 22 of 58 patients showed a > or = 2-fold increase in intracellular growth compared with control macrophages. Thus, in addition to defects in cell-mediated immunity caused by a loss of CD4+ T cells, macrophages from HIV-positive patients exhibit intrinsic defects in macrophage function against H. capsulatum that may contribute to the increased susceptibility of HIV-positive patients to disseminated histoplasmosis.
Insights
Macrophages from people with human immunodeficiency virus (HIV) show impaired recognition and binding of Histoplasma capsulatum. These immune cells also allow increased fungal growth, contributing to disseminated histoplasmosis risk.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Human immunodeficiency virus (HIV) infection severely impacts the immune system, particularly CD4+ T cells.
- Disseminated histoplasmosis is a serious opportunistic infection, especially in immunocompromised individuals.
- Macrophages play a critical role in controlling fungal infections like histoplasmosis.
Purpose of the Study:
- To investigate the phagocytic and fungistatic activity of monocyte-derived macrophages from HIV-positive individuals against Histoplasma capsulatum.
- To determine if intrinsic macrophage defects contribute to susceptibility to histoplasmosis in HIV patients.
Main Methods:
- Monocyte-derived macrophages were isolated from HIV-positive patients and healthy controls.
- Phagocytic activity (recognition, binding, ingestion) against Histoplasma capsulatum yeasts was assessed.
- Intracellular growth of H. capsulatum within macrophages was quantified.
- Correlation with CD4+ T lymphocyte counts was analyzed.
Main Results:
- Macrophages from HIV-positive patients exhibited significantly reduced ability to recognize and bind H. capsulatum.
- Ingestion of bound H. capsulatum was normal, indicating a specific defect in initial recognition.
- Macrophage binding capacity correlated inversely with CD4+ T lymphocyte counts.
- A substantial proportion of patient macrophages (22/58) showed increased permissiveness for intracellular H. capsulatum growth.
Conclusions:
- HIV-positive patients exhibit intrinsic macrophage functional defects against H. capsulatum, beyond CD4+ T cell depletion.
- These macrophage defects, including impaired fungal recognition and enhanced intracellular growth, likely contribute to increased susceptibility to disseminated histoplasmosis.