Related Experiment Videos
Monocyte dysfunction in patients with acquired immunodeficiency syndrome (AIDS) versus Cryptococcus neoformans
C Monari1, F Baldelli, D Pietrella
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Abstract:
In the present study we investigated the response of monocytes from AIDS patients, susceptible to cryptococcosis (<200 CD4 cells/microl), against Cryptococcus neoformans. Different patterns of response were observed in these cells compared to cells from healthy donors. In particular, fungicidal activity versus this fungus was impaired; this phenomenon could be due to the difficulty of monocytes to internalize C. neoformans in the presence of an intact complement system. Impairment of complement receptor type 3 and direct involvement of this receptor in phagocytosis of C. neoformans were found in monocytes from AIDS patients, which may account for the difficulty in phagocytosis of the fungus. Also, superoxide anion production was dramatically reduced in monocytes from AIDS patients. An increase of spontaneous tumor necrosis factor (TNF) production was evidenced after in vitro addition of C. neoformans. However, this did not activate the antifungal capacity of monocytes from AIDS patients. Moreover, cryptococcus-laden monocytes from AIDS patients were able to induce only a weak response of autologous T-lymphocytes. Hence, monocyte dysfunction could play a part in the progression of cryptococcosis in AIDS.
Insights
Monocytes from AIDS patients show impaired antifungal activity against Cryptococcus neoformans, struggling with fungal uptake and T-lymphocyte response, contributing to cryptococcosis progression.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- AIDS patients with low CD4 counts are susceptible to opportunistic infections like cryptococcosis.
- Monocytes play a crucial role in the immune response against fungal pathogens.
Purpose of the Study:
- To investigate the functional response of monocytes from AIDS patients against Cryptococcus neoformans.
- To identify specific defects in monocyte function that may contribute to cryptococcosis.
Main Methods:
- Comparison of monocyte responses (phagocytosis, superoxide production, TNF-alpha release) from AIDS patients and healthy donors.
- Assessment of Cryptococcus neoformans internalization by monocytes.
- Evaluation of T-lymphocyte activation by cryptococcus-laden monocytes.
Main Results:
- Monocytes from AIDS patients exhibited impaired fungicidal activity against C. neoformans.
- Reduced phagocytosis of C. neoformans by AIDS patient monocytes, linked to complement receptor type 3 dysfunction.
- Significantly decreased superoxide anion production and a weak T-lymphocyte response induced by cryptococcus-laden monocytes.
Conclusions:
- Monocyte dysfunction, including impaired phagocytosis and reduced microbicidal activity, contributes to cryptococcosis susceptibility in AIDS patients.
- Defective complement receptor type 3 function is implicated in the phagocytic defect.
- These monocyte defects may play a role in the progression of cryptococcosis in individuals with advanced HIV infection.