ArticleInfection and immunity2013
Requirement and redundancy of the Src family kinases Fyn and Lyn in perforin-dependent killing of Cryptococcus neoformans by NK cells.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
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- Transcriptomic and proteomic signatures of host NK cells delineate distinct immune states across tuberculosis infection statuses.Frontiers in immunology · 2025Article
- State of the Field: Cytotoxic Immune Cell Responses inJournal of fungi (Basel, Switzerland) · 2024Review
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- Natural Killer Cells and Cytotoxic T Cells: Complementary Partners against Microorganisms and Cancer.Microorganisms · 2024Review
- Targeting natural killer cells to enhance vaccine responses.Trends in pharmacological sciences · 2021Review
- Computational Prediction of Biomarkers, Pathways, and New Target Drugs in the Pathogenesis of Immune-Based Diseases Regarding Kidney Transplantation Rejection.Frontiers in immunology · 2021Article
- TICAM2-related pathway mediates neutrophil exhaustion.Scientific reports · 2020Article
- A dynamic transcriptomic atlas of cytokine-induced killer cells.The Journal of biological chemistry · 2018Article
- Lymphocyte-Specific Protein Tyrosine Kinase (LCK) is Involved in the Aryl Hydrocarbon Receptor-Mediated Impairment of Immunoglobulin Secretion in Human Primary B Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida.Nature communications · 2018Article
- Regulation of C-Type Lectin Receptor-Mediated Antifungal Immunity.Frontiers in immunology · 2018Review
- Article
- Ras-related C3 Botulinum Toxin Substrate (Rac) and Src Family Kinases (SFK) Are Proximal and Essential for Phosphatidylinositol 3-Kinase (PI3K) Activation in Natural Killer (NK) Cell-mediated Direct Cytotoxicity against Cryptococcus neoformans.The Journal of biological chemistry · 2016Article
- Innate host defenses against Cryptococcus neoformans.Journal of microbiology (Seoul, Korea) · 2016Review
- Signaling in Effector Lymphocytes: Insights toward Safer Immunotherapy.Frontiers in immunology · 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
- STAT1 signaling within macrophages is required for antifungal activity against Cryptococcus neoformans.Infection and immunity · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Natural killer (NK) cells directly recognize and kill fungi, such as the pathogenic fungus Cryptococcus neoformans, via cytolytic mechanisms. However, the precise signaling pathways governing this NK cell microbicidal activity and the implications for fungal recognition are still unknown. Previously, it was reported that NK cell anticryptococcal activity is mediated through a conserved phosphatidylinositol 3-kinase-extracellular signal-regulated kinase 1/2 (PI3K-ERK1/2) pathway. Using YT (a human NK-like cell line) and primary human NK cells, we sought to identify the upstream, receptor-proximal signaling elements that led to fungal cytolysis. We demonstrate that Src family kinases were activated in response to C. neoformans. Furthermore, pharmacologic inhibition with an Src kinase inhibitor blocked C. neoformans-induced downstream activation of PI3K and ERK1/2 and abrogated cryptococcal killing. At the same time, the inhibitor disrupted the polarization of perforin-containing granules toward the NK cell-cryptococcal synapse but had no effect on conjugate formation between the organism and the NK cell. Finally, small interfering RNA (siRNA) double (but not single) knockdown of two Src family kinases, Fyn and Lyn, blocked cryptococcal killing. Together these data demonstrate a mechanism whereby the Src family kinases, Fyn and Lyn, redundantly mediate anticryptococcal activity through the activation of PI3K and ERK1/2, which in turn facilitates killing by inducing the polarization of perforin-containing granules to the NK cell-cryptococcal synapse.
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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.