ArticleInfection and immunity1999
Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages.
Article in Infection and immunity, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed, 237 citations in OpenAlex.
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- Elements of dissemination in cryptococcosis.mBio · 2024Review
- Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities.Nature microbiology · 2024Review
- Natural compounds from freshwater mussels disrupt fungal virulence determinants and influence fluconazole susceptibility in the presence of macrophages inMicrobiology spectrum · 2024Article
- The emerging links between immunosenescence in innate immune system and neurocryptococcosis.Frontiers in immunology · 2024Review
- Dendritic Cells: Multifunctional Roles in Host Defenses toJournal of fungi (Basel, Switzerland) · 2023Review
- Fungal mechanisms of intracellular survival: what can we learn from bacterial pathogens?Infection and immunity · 2023Review
- Innate Pulmonary Phagocytes and Their Interactions with PathogenicJournal of fungi (Basel, Switzerland) · 2023Review
- More than Just Protein Degradation: The Regulatory Roles and Moonlighting Functions of Extracellular Proteases Produced by Fungi Pathogenic for Humans.Journal of fungi (Basel, Switzerland) · 2023Review
- Mouse Model of Latent Cryptococcal Infection and Reactivation.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The nature of the fungal cargo induces significantly different temporal programmes of macrophage phagocytosis.Cell surface (Amsterdam, Netherlands) · 2022Article
- Host immune responses in the central nervous system during fungal infections.Immunological reviews · 2022Review
- Bet-hedging antimicrobial strategies in macrophage phagosome acidification drive the dynamics of Cryptococcus neoformans intracellular escape mechanisms.PLoS pathogens · 2022Article
- Real-time visualization of phagosomal pH manipulation byFrontiers in cellular and infection microbiology · 2022Article
77 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
Recently, we demonstrated that human monocyte-derived macrophages (MDM) treated with chloroquine or ammonium chloride had markedly increased antifungal activity against the AIDS-related pathogen Cryptococcus neoformans. Both of these agents raise the lysosomal pH, which suggested that the increased antifungal activity was a function of alkalinizing the phagolysosome. Moreover, there was an inverse correlation between growth of C. neoformans in cell-free media and pH. These data suggested that C. neoformans was well adapted to survive within acidic compartments. To test this hypothesis, we performed studies to determine the pH of human MDM and neutrophil phagosomes containing C. neoformans. Fungi were labeled with the isothiocyanate derivatives of two pH-sensitive probes: fluorescein and 2',7'-difluorofluorescein (Oregon Green). These probes have pKas of 6.4 and 4.7, respectively, allowing sensitive pH detection over a broad range. The phagosomal pH averaged approximately 5 after ingestion of either live or heat-killed fungi and remained relatively constant over time, which suggested that C. neoformans does not actively regulate the pH of its phagosome. The addition of 10 and 100 microM chloroquine resulted in increases in the phagosomal pH from a baseline of 5.1 up to 6.5 and 7.3, respectively. Finally, by immunofluorescence, colocalization of C. neoformans and the MDM lysosomal membrane protein LAMP-1 was demonstrated, establishing that fusion of C. neoformans-laden phagosomes with lysosomal compartments takes place. Thus, unlike many other intracellular pathogens, C. neoformans does not avoid fusion with macrophage lysosomal compartments but rather resides and survives in an acidic phagolysosome.
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