ArticleNature medicine2016
Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 195 citations in OpenAlex.
- In Situ Cellular Response Underlying Successful Treatment of Mucosal Leishmaniasis with a Combination of Pentavalent Antimonial and Pentoxifylline.The American journal of tropical medicine and hygiene · 2019Trial
- Antileishmanial potential of polar fractions from Amaranthus blitoides S. Watson, Caucalis platycarpos L., and Cistanche flava (C.A.Mey.) Korsh.: evidence from in vitro and in vivo studies.Tropical medicine and health · 2026Article
- Rickettsial Diseases and Vaccines: Is There an Opportunity for Plant-Made Vaccine Technology?Biotechnology and bioengineering · 2026Review
- Single-cell profiling of peripheral blood reveals acute-phase immune dysregulation in human scrub typhus.iMeta · 2026Article
- A cDC1-NK/T-Malignant Cell Circuit Drives Immunogenic Remodeling Under PD-1 Blockade in Gastric Cancer.Cancer science · 2026Article
- Menstruation is Associated With Cyclical Granulysin Peaks in Vaginal Secretions Despite Stable Expression by Cervicovaginal Immune Cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- Rickettsiosis: existing advances and future opportunities for the development of vaccines.Veterinary research communications · 2026Review
- ATG5 Plays a Role inTransboundary and emerging diseases · 2026Article
- Apoptosis as an evolutionary battleground: pathogen pressure and the shaping of programmed cell death pathways.Frontiers in cell and developmental biology · 2026Review
- CD160 mediated NK cell activation shapes host defense against acuteFrontiers in immunology · 2026Article
- The mechanism regulating the cytotoxicity of γδ T cells activated by mycobacterium tuberculosis heat-resistant antigen based on RNA-seq analysis.Frontiers in immunology · 2026Article
- Endogenous Amphiregulin promotes muscle repair and function through expansion of fibro-adipogenic progenitors during chronicFrontiers in microbiology · 2026Article
- Reprogramming natural killer cells in the tumor microenvironment: Challenges and therapeutic opportunities.Cytokine & growth factor reviews · 2025Review
- Article
- Antibody-Mediated In Vitro Activation and Expansion of Blood Donor-Derived Natural Killer Cells with Transient Anti-Tumor Efficacy.Biomedicines · 2025Article
- Disrupting membranes, controlling cell fate: the role of pore-forming proteins in cell death and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Serum Granulysin Levels in Vitiligo and Alopecia Areata: A Potential Biomarker for Disease Activity and Dermoscopic Evaluation.Journal of clinical medicine · 2025Article
- scIVNL-seq resolves in vivo single-cell RNA dynamics of immune cells during Salmonella infection.Nature communications · 2025Article
- Granulysin-high decidual NK cells in macaques and humans share signatures of immune defense.Cell reports · 2025Article
- The time has come for a vaccine against Chagas disease.Lancet regional health. Americas · 2025Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Protozoan infections are a serious global health problem. Natural killer (NK) cells and cytolytic T lymphocytes (CTLs) eliminate pathogen-infected cells by releasing cytolytic granule contents--granzyme (Gzm) proteases and the pore-forming perforin (PFN)--into the infected cell. However, these cytotoxic molecules do not kill intracellular parasites. CD8(+) CTLs protect against parasite infections in mice primarily by secreting interferon (IFN)-γ. However, human, but not rodent, cytotoxic granules contain the antimicrobial peptide granulysin (GNLY), which selectively destroys cholesterol-poor microbial membranes, and GNLY, PFN and Gzms rapidly kill intracellular bacteria. Here we show that GNLY delivers Gzms into three protozoan parasites (Trypanosoma cruzi, Toxoplasma gondii and Leishmania major), in which the Gzms generate superoxide and inactivate oxidative defense enzymes to kill the parasite. PFN delivers GNLY and Gzms into infected cells, and GNLY then delivers Gzms to the intracellular parasites. Killer cell-mediated parasite death, which we term 'microbe-programmed cell death' or 'microptosis', is caspase independent but resembles mammalian apoptosis, causing mitochondrial swelling, transmembrane potential dissipation, membrane blebbing, phosphatidylserine exposure, DNA damage and chromatin condensation. GNLY-transgenic mice are protected against infection by T. cruzi and T. gondii, and survive infections that are lethal to wild-type mice. Thus, GNLY-, PFN- and Gzm-mediated elimination of intracellular protozoan parasites is an unappreciated immune defense mechanism.
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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.