ArticleInfection and immunity2009
Cryptococcus neoformans directly stimulates perforin production and rearms NK cells for enhanced anticryptococcal microbicidal activity.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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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
33 citing papers in PubMed, 54 citations in OpenAlex.
- Human natural killer cells exhibit potent antifungal activity against azole-resistantMicrobiology spectrum · 2026Article
- Calcium transport systems as virulence determinants: Mechanistic insights into fungal pathogenicity and antifungal resistance.Virulence · 2025Review
- State of the Field: Cytotoxic Immune Cell Responses inJournal of fungi (Basel, Switzerland) · 2024Review
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- Innate Pulmonary Phagocytes and Their Interactions with PathogenicJournal of fungi (Basel, Switzerland) · 2023Review
- Transcriptional Profiles Elucidate Differential Host Responses to Infection withJournal of fungi (Basel, Switzerland) · 2022Article
- Subdiffraction-resolution fluorescence imaging of immunological synapse formation between NK cells and A. fumigatus by expansion microscopy.Communications biology · 2021Article
- Immune Cell Degranulation in Fungal Host Defence.Journal of fungi (Basel, Switzerland) · 2021Review
- Airway Natural Killer Cells and Bacteria in Health and Disease.Frontiers in immunology · 2020Review
- Human NK cells adapt their immune response towards increasing multiplicities of infection of Aspergillus fumigatus.BMC immunology · 2018Article
- Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida.Nature communications · 2018Article
- Innate immune evasion strategies against Cryptococcal meningitis caused byExperimental and therapeutic medicine · 2017Article
- Host response to pulmonary fungal infections: A highlight on cell-driven immunity toCurrent pharmacology reports · 2017Article
- NK Cells and Their Role in Invasive Mold Infection.Journal of fungi (Basel, Switzerland) · 2017Review
- Natural Killer Cells in Antifungal Immunity.Frontiers in immunology · 2017Review
- Article
- Innate host defenses against Cryptococcus neoformans.Journal of microbiology (Seoul, Korea) · 2016Review
- TNFα Augments Cytokine-Induced NK Cell IFNγ Production through TNFR2.Journal of innate immunity · 2016Article
- Granule-Dependent Natural Killer Cell Cytotoxicity to Fungal Pathogens.Frontiers in immunology · 2016Review
- Immunity to Cryptococcus neoformans and C. gattii during cryptococcosis.Fungal genetics and biology : FG & B · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NK cells, in addition to possessing antitumor and antiviral activity, exhibit perforin-dependent microbicidal activity against the opportunistic pathogen Cryptococcus neoformans. However, the factors controlling this response, particularly whether the pathogen itself provides an activation or rearming signal, are largely unknown. The current studies were performed to determine whether exposure to this fungus alters subsequent NK cell anticryptococcal activity. NK cells lost perforin and mobilized lysosome-associated membrane protein 1 to the cell surface following incubation with the fungus, indicating that degranulation had occurred. Despite a reduced perforin content during killing, NK cells acquired an enhanced ability to kill C. neoformans, as demonstrated using auxotrophs that allowed independent assessment of the killing of two strains. De novo protein synthesis was required for optimal killing; however, there was no evidence that a soluble factor contributed to the enhanced anticryptococcal activity. Exposure of NK cells to C. neoformans caused the cells to rearm, as demonstrated by increased perforin mRNA levels and enhanced loss of perforin when transcription was blocked. Degranulation alone was insufficient to provide the activation signal as NK cells lost anticryptococcal activity following treatment with strontium chloride. However, NK cells regained the activity upon prolonged exposure to C. neoformans, which is consistent with activation by the microbe. The enhanced cytotoxicity did not extend to tumor killing since NK cells exposed to C. neoformans failed to kill NK-sensitive tumor targets (K562 cells). These studies demonstrate that there is contact-mediated microbe-specific rearming and activation of microbicidal activity that are necessary for optimal killing of C. neoformans.
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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.