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Human immunodeficiency virus type 1 envelope protein gp120 impairs intracellular antifungal mechanisms in human
D Pietrella1, C Monari, C Retini
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Abstract:
The key to success of fungal opportunistic pathogens in the immunocompromised host is related to survival inside phagocytic cells, which represent the first line of defense against microorganisms. The contribution of human immunodeficiency virus-1 recombinant envelope protein gp120 on effector functions of peripheral blood monocytes (PBM) against Candida albicans was investigated. gp120 binds CD4 receptors on PBM while not affecting the access of the fungus into the lysosome compartment. However, gp120 reduces the antifungal capacity of PBM. This phenomenon correlates with impaired oxygen-dependent antimicrobial machinery and reduced ability of phagolysosome acidification. The maintenance of phagolysosomal pH at approximately 6.2 restricts antimicrobial properties of the enzyme that work at a low pH, as evidenced by reduced antifungal capability of lysosomal protein extracted from gp120-treated PBM. These findings highlight gp120 perturbation of intracellular antimicrobial mechanisms of phagocytic cells and suggest a new aspect for gp120 in impairing immune functions.
Insights
Human immunodeficiency virus-1 envelope protein gp120 impairs the antifungal functions of human peripheral blood monocytes (PBM). This impairment is linked to reduced phagolysosome acidification and oxygen-dependent antimicrobial activity against Candida albicans.
Area of Science:
- Immunology
- Mycology
- Virology
Background:
- Fungal opportunistic pathogens thrive in immunocompromised hosts by evading phagocytic cells.
- Human immunodeficiency virus-1 (HIV-1) infection compromises immune defenses, increasing susceptibility to such pathogens.
Purpose of the Study:
- To investigate the impact of HIV-1 recombinant envelope protein gp120 on the antifungal functions of peripheral blood monocytes (PBM) against Candida albicans.
- To elucidate the mechanisms by which gp120 affects PBM's ability to combat fungal infections.
Main Methods:
- Peripheral blood monocytes (PBM) were treated with gp120.
- The interaction of Candida albicans with gp120-treated PBM was assessed.
- Phagolysosome acidification and oxygen-dependent antimicrobial activity were measured.
- Antifungal capacity of lysosomal proteins was evaluated.
Main Results:
- gp120 binds to CD4 receptors on PBM without preventing fungal entry into lysosomes.
- gp120 significantly reduces the antifungal capacity of PBM against Candida albicans.
- This reduction correlates with impaired oxygen-dependent antimicrobial machinery.
- Reduced phagolysosome acidification was observed, hindering the efficacy of pH-dependent enzymes.
Conclusions:
- HIV-1 gp120 directly impairs the intracellular antimicrobial mechanisms of phagocytic cells like PBM.
- gp120's disruption of phagolysosome function represents a novel mechanism by which HIV-1 compromises host immunity against fungal infections.