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Granulysin: killer lymphocyte safeguard against microbes.

Abstract

Primary T cell immunodeficiency and HIV-infected patients are plagued by non-viral infections caused by bacteria, fungi, and parasites, suggesting an important and underappreciated role for T lymphocytes in controlling microbes. Here, we review recent studies showing that killer lymphocytes use the antimicrobial cytotoxic granule pore-forming peptide granulysin, induced by microbial exposure, to permeabilize cholesterol-poor microbial membranes and deliver death-inducing granzymes into these pathogens. Granulysin and granzymes cause microptosis, programmed cell death in microbes, by inducing reactive oxygen species and destroying microbial antioxidant defenses and disrupting biosynthetic and central metabolism pathways required for their survival, including protein synthesis, glycolysis, and the Krebs cycle.

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  • Authors+Show Affiliations

    ,

    The Wistar Institute, Vaccine and Immunotherapy Center, Philadelphia, PA 19104, USA.

    Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: judy.lieberman@childrens.harvard.edu.

    Source

    Current opinion in immunology 60: 2019 May 18 pg 19-29

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    31112765

    Citation

    Dotiwala, Farokh, and Judy Lieberman. "Granulysin: Killer Lymphocyte Safeguard Against Microbes." Current Opinion in Immunology, vol. 60, 2019, pp. 19-29.
    Dotiwala F, Lieberman J. Granulysin: killer lymphocyte safeguard against microbes. Curr Opin Immunol. 2019;60:19-29.
    Dotiwala, F., & Lieberman, J. (2019). Granulysin: killer lymphocyte safeguard against microbes. Current Opinion in Immunology, 60, pp. 19-29. doi:10.1016/j.coi.2019.04.013.
    Dotiwala F, Lieberman J. Granulysin: Killer Lymphocyte Safeguard Against Microbes. Curr Opin Immunol. 2019 May 18;60:19-29. PubMed PMID: 31112765.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Granulysin: killer lymphocyte safeguard against microbes. AU - Dotiwala,Farokh, AU - Lieberman,Judy, Y1 - 2019/05/18/ PY - 2019/03/05/received PY - 2019/04/15/revised PY - 2019/04/16/accepted PY - 2019/5/22/pubmed PY - 2019/5/22/medline PY - 2019/5/22/entrez SP - 19 EP - 29 JF - Current opinion in immunology JO - Curr. Opin. Immunol. VL - 60 N2 - Primary T cell immunodeficiency and HIV-infected patients are plagued by non-viral infections caused by bacteria, fungi, and parasites, suggesting an important and underappreciated role for T lymphocytes in controlling microbes. Here, we review recent studies showing that killer lymphocytes use the antimicrobial cytotoxic granule pore-forming peptide granulysin, induced by microbial exposure, to permeabilize cholesterol-poor microbial membranes and deliver death-inducing granzymes into these pathogens. Granulysin and granzymes cause microptosis, programmed cell death in microbes, by inducing reactive oxygen species and destroying microbial antioxidant defenses and disrupting biosynthetic and central metabolism pathways required for their survival, including protein synthesis, glycolysis, and the Krebs cycle. SN - 1879-0372 UR - https://www.unboundmedicine.com/medline/citation/31112765/Granulysin:_killer_lymphocyte_safeguard_against_microbes L2 - https://linkinghub.elsevier.com/retrieve/pii/S0952-7915(19)30017-2 DB - PRIME DP - Unbound Medicine ER -