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Dysregulation of the polymorphonuclear leukocyte--Candida spp. interaction in HIV-positive patients
C Wenisch1, B Parschalk, K Zedwitz-Liebenstein
1Department of Infectious Diseases, University Hospital of Vienna, Austria.
Objective:
In HIV-infected patients there is an increased frequency of fungal infections. Dysregulation of the response of phagocytic cells to fungal pathogens may be involved.
Design:
Phagocytosis of Candida spp., consecutive intracellular production of reactive oxygen species, and candicidal activity were analysed in polymorphonuclear leukocytes (PML) from HIV-1-infected patients, who were at stage C3 of the 1993 revised Centers for Disease Control and Prevention classification system, by means of flow cytometry.
Methods:
Phagocytic ability was assessed by measuring uptake of fluorescein isothiocyanate-labelled Candida albicans, C. krusei and C. glabrata. Reactive oxygen intermediate production was estimated by the quantity of dihydrorhodamine-123 converted to rhodamine-123 intracellularly. The candicidal effect was assessed by the propidium iodide uptake of killed yeast cells.
Results:
As compared to PML of healthy, HIV-negative controls, PML of AIDS patients exhibited an increased phagocytic activity and a similar ability to generate reactive oxygen products. In contrast, PML of AIDS patients displayed a decreased candicidal activity (P < 0.05 compared to controls).
Conclusion:
These results suggest that in patients with advanced HIV-1 infection the impairment of non-oxidative killing mechanisms of phagocytic cells may contribute to the high incidence of fungal infections.
Insights
Polymorphonuclear leukocytes (PML) from advanced HIV-1 infected patients show increased phagocytosis but impaired fungal killing. This suggests non-oxidative mechanisms may be key in increased fungal infections in AIDS patients.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- HIV-1 infection is associated with a higher incidence of fungal infections.
- Dysregulation in phagocytic cell responses to fungi may contribute to increased susceptibility.
Purpose of the Study:
- To investigate the phagocytic cell function in HIV-1 infected patients.
- To analyze the phagocytosis, reactive oxygen species production, and candicidal activity of polymorphonuclear leukocytes (PML) in advanced HIV-1 infection.
Main Methods:
- Flow cytometry was used to analyze PML from HIV-1 infected patients (CDC stage C3) and healthy controls.
- Phagocytic activity was measured by uptake of labeled Candida species.
- Intracellular reactive oxygen intermediate production and candicidal activity were assessed.
Main Results:
- PML from AIDS patients demonstrated enhanced phagocytic activity compared to controls.
- The ability to generate reactive oxygen products was similar between AIDS patients and controls.
- Candicidal activity was significantly reduced in PML from AIDS patients (P < 0.05).
Conclusions:
- Impaired non-oxidative killing mechanisms in phagocytic cells may contribute to fungal infections in advanced HIV-1 disease.
- These findings highlight a potential mechanism for increased fungal susceptibility in immunocompromised individuals.