PHAGOCYTOSIS AND GROWTH-INHIBITION OF CRYPTOCOCCUS-NEOFORMANS BY HUMAN ALVEOLAR MACROPHAGES - EFFECTS OF HIV-1 INFECTION

Objective: The purpose of this study was to investigate the in vitro p rocessing of Cryptococcus neoformans by human alveolar macrophages fro m HIV-seropositive individuals compared with HIV-seronegative individu als. Design and methods: Bronchoalveolar 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. neo formans and assessed for fungal binding, phagocytosis, and growth inhi bition. Results: The results indicated that BAL cells from the smoking HIV-infected group had increased fungistatic activity compared with H IV-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 C 3) 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 r ecovered from HIV-seronegative smoking volunteers demonstrated reduced fungistatic activity when compared with BAL cells from HIV-seronegati ve nonsmokers (56.8 +/- 8.8 versus 83.0 +/- 2.2%; P < 0.001). Smoking also induced a decrease in internalization of C. neoformans by alveola r macrophages as assessed by confocal laser microscopy in both HIV-ser onegative and HIV-infected groups. Conclusion: We conclude that BAL ce lls from early-stage HIV-1-infected individuals do not have an intrins ic defect in fungistasis of C. neoformans. In fact, it appears that BA L cells from HIV-seropositive people are activated far fungistasis in early HIV infection, although fungistatic activity declines as the dis ease progresses. Incidentally noted was the finding that smoking decre ases the internalization of C. neoformans in both HIV-infected and HIV -seronegative individuals, suggesting the possibility that smoking mig ht enhance the susceptibility to cryptococcosis.