Phagocytosis and growth inhibition of Cryptococcus neoformans by human alveolar macrophages: effects of HIV-1 infection.

ABSTRACT

OBJECTIVE: The purpose of this study was to investigate the in vitro processing of Cryptococcus neoformans by human alveolar macrophages from HIV-seropositive individuals compared with HIV-seronegative individuals. DESIGN AND METHODS: Bronchalveolar lavage (BAL) was performed on smoking and nonsmoking HIV-seropositive and seronegative volunteers. Lavage cells from the four groups were challenged in vitro with C. neoformans and assessed for fungal binding, phagocytosis, and growth inhibition. RESULTS: The results indicated that BAL cells from the smoking HIV-infected group had increased fungistatic activity compared with HIV-seronegative smokers (mean percentage growth inhibition +/- SD, 77.5 +/- 14.2 versus 59.1 +/- 16.6%; P = 0.015). However, late-staged HIV-infected patients (Centers for Disease Control and Prevention class C3) were found to have decreased fungistasis compared with early stage A patients (63.8 +/- 11.1 versus 83.0 +/- 2.2%; P < 0.05). BAL cells recovered from HIV- seronegative smoking volunteers demonstrated reduced fungistatic activity when compared with BAL cells from HIV- seronegative nonsmokers (56.8 +/- 8.8 versus 83.0 +/- 2.2%; P < 0.001). Smoking also induced a decrease in internalization of C. neoformans by alveolar macrophages as assessed by confocal laser microscopy in both HIV-seronegative and HIV-infected groups. CONCLUSION: We conclude that BAL cells from early stage HIV-1-infected individuals do not have an intrinsic defect in fungistasis of C. neoformans. In fact, it appears that BAL cells from HIV-seropositive people are activated for fungistasis in early HIV infection, although fungistatic activity declines as the disease progresses. Incidentally noted was the finding that smoking decreases the internalization of C. neoformans in both HIV-infected and HIV-seronegative individuals, suggesting the possibility that smoking might enhance the susceptibility to cryptococcosis.