ArticleBMC immunology2007
Perforin enhances the granulysin-induced lysis of Listeria innocua in human dendritic cells.
Article in BMC immunology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- CTLs: Killers of intracellular bacteria.Frontiers in cellular and infection microbiology · 2022Review
- CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn's disease.Nature communications · 2021Article
- A Profound Membrane Reorganization Defines Susceptibility ofFrontiers in immunology · 2021Article
- Oxidative and Non-Oxidative Antimicrobial Activities of the Granzymes.Frontiers in immunology · 2021Review
- γδ T Cells KillJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Article
- Perforin Acts as an Immune Regulator to Prevent the Progression of NAFLD.Frontiers in immunology · 2020Article
- Granulysin: killer lymphocyte safeguard against microbes.Current opinion in immunology · 2019Review
- IL-26 contributes to host defense against intracellular bacteria.The Journal of clinical investigation · 2019Article
- Analysis of granulysin-mediated cytotoxicity in peripheral blood of patients with psoriatic arthritis.Rheumatology international · 2012Article
- Cell death mechanisms at the maternal-fetal interface: insights into the role of granulysin.Clinical & developmental immunology · 2012Review
- Leishmania-infected macrophages are targets of NK cell-derived cytokines but not of NK cell cytotoxicity.Infection and immunity · 2011Article
- Direct microbicidal activity of cytotoxic T-lymphocytes.Journal of biomedicine & biotechnology · 2010Review
- Comparative antimicrobial activity of granulysin against bacterial biothreat agents.The open microbiology journal · 2009Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCytotoxic T lymphocytes (CTL) and natural killer (NK) cells play an essential role in the host defence against intracellular pathogens such as Listeria, and Mycobacteria. The key mediator of bacteria-directed cytotoxicity is granulysin, a 9 kDa protein stored in cytolytic granules together with perforin and granzymes. Granulysin binds to cell membranes and is subsequently taken up via a lipid raft-associated mechanism. In dendritic cells (DC) granulysin is further transferred via early endosomes to L. innocua-containing phagosomes were bacteriolysis is induced. In the present study we analysed the role of perforin in granulysin-induced intracellular bacteriolysis in DC.
resultsWe found granulysin-induced lysis of intracellular Listeria significantly increased when perforin was simultaneously present. In pulse-chase experiments enhanced bacteriolysis was observed when perforin was added up to 25 minutes after loading the cells with granulysin demonstrating no ultimate need for simultaneous uptake of granulysin and perforin. The perforin concentration sufficient to enhance granulysin-induced intracellular bacteriolysis did not cause permanent membrane pores in Listeria-challenged DC as shown by dye exclusion test and LDH release. This was in contrast to non challenged DC that were more susceptible to perforin lysis. For Listeria-challenged DC, there was clear evidence for an Ca2+ influx in response to sublytic perforin demonstrating a short-lived change in the plasma membrane permeability. Perforin treatment did not affect granulysin binding, initial uptake or intracellular trafficking to early endosomes. However, enhanced colocalization of granulysin with listerial DNA in presence of perforin was found by confocal laser scanning microscopy.
conclusionThe results provide evidence that perforin increases granulysin-mediated killing of intracellular Listeria by enhanced phagosome-endosome fusion triggered by a transient Ca2+ flux.
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Registered trials
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