ArticleThe Journal of clinical investigation1997
Chloroquine induces human mononuclear phagocytes to inhibit and kill Cryptococcus neoformans by a mechanism independent of iron deprivation.
Article in The Journal of clinical investigation, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 124 citations in OpenAlex.
- Effects of Ammonium Chloride-Mediated Control of Digestive Vacuole Acidification on Endosymbiosis BetweenMicroorganisms · 2026Article
- A review of the current anti-New microbes and new infections · 2026Review
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- A trade-off between proliferation and defense in the fungal pathogenbioRxiv : the preprint server for biology · 2024Article
- A Multi-Fluorophore Staining Scheme for Identification and Quantification of Vomocytosis.Chemical & biomedical imaging · 2023Article
- In vitro and in vivo synergistic effects of hydroxychloroquine and itraconazole on Cryptococcus neoformans.Folia microbiologica · 2023Article
- Identification and Elimination of Antifungal Tolerance inBiomedicines · 2023Article
- Reciprocal modulation of ammonia and melanin production has implications for cryptococcal virulence.Nature communications · 2023Article
- 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
- Deficiency of lung-specific claudin-18 leads to aggravated infection with Cryptococcus deneoformans through dysregulation of the microenvironment in lungs.Scientific reports · 2021Article
- Article
- Mechanisms of fungal dissemination.Cellular and molecular life sciences : CMLS · 2021Review
- A review on possible modes of action of chloroquine/hydroxychloroquine: repurposing against SAR-CoV-2 (COVID-19) pandemic.International journal of antimicrobial agents · 2020Review
- Pulmonary Macrophage and Dendritic Cell Responses toFrontiers in cellular and infection microbiology · 2020Review
- Nonlytic exocytosis of Cryptococcus neoformans from neutrophils in the brain vasculature.Cell communication and signaling : CCS · 2019Article
- Article
- Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review.Clinical drug investigation · 2018Review
- Cryptococcus neoformans urease affects the outcome of intracellular pathogenesis by modulating phagolysosomal pH.PLoS pathogens · 2018Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Infections due to Cryptococcus neoformans are common in AIDS patients. We investigated the effect of chloroquine, which raises the pH of phagolysosomes, on the anticryptococcal activity of mononuclear phagocytes. C. neoformans multiplied within monocyte-derived macrophages (MDM) in the absence of chloroquine but were killed with the addition of chloroquine. Ammonium chloride was also beneficial, suggesting that effects were mediated by alkalinizing the phagolysosome. Chloroquine inhibits growth of other intracellular pathogens by limiting iron availability. However, chloroquine-induced augmentation of MDM anticryptococcal activity was unaffected by iron nitriloacetate, demonstrating that chloroquine worked by a mechanism independent of iron deprivation. There was an inverse correlation between growth of C. neoformans in cell-free media and pH, suggesting that some of the effect of chloroquine on the anticryptococcal activity of MDM could be explained by relatively poor growth at higher pH. Chloroquine enhanced MDM anticryptococcal activity against all tested cryptococcal strains except for one large-capsule strain which was not phagocytosed. Positive effects of chloroquine were also seen in monocytes from both HIV-infected and -uninfected donors. Finally, chloroquine was therapeutic in experimental cryptococcosis in outbred and severe combined immunodeficient mice. Thus, chloroquine enhances the activity of mononuclear phagocytes against C. neoformans by iron-independent, pH-dependent mechanisms and is therapeutic in murine models of cryptococcosis. Chloroquine might have clinical utility for the prophylaxis and treatment of human cryptococcosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.