Abstract
Cell-mediated cytotoxicity is an essential immune defense mechanism to fight against viral, bacterial or parasitic infections. Upon recognition of an infected target cell, killer lymphocytes form an immunological synapse to release the content of their cytotoxic granules. Cytotoxic granules of humans contain two membrane-disrupting proteins, perforin and granulysin, as well as a homologous family of five death-inducing serine proteases, the granzymes. The granzymes, after delivery into infected host cells by the membrane disrupting proteins, may contribute to the clearance of microbial pathogens through different mechanisms. The granzymes can induce host cell apoptosis, which deprives intracellular pathogens of their protective niche, therefore limiting their replication. However, many obligate intracellular pathogens have evolved mechanisms to inhibit programed cells death. To overcome these limitations, the granzymes can exert non-cytolytic antimicrobial activities by directly degrading microbial substrates or hijacked host proteins crucial for the replication or survival of the pathogens. The granzymes may also attack factors that mediate microbial virulence, therefore directly affecting their pathogenicity. Many mechanisms applied by the granzymes to eliminate infected cells and microbial pathogens rely on the induction of reactive oxygen species. These reactive oxygen species may be directly cytotoxic or enhance death programs triggered by the granzymes. Here, in the light of the latest advances, we review the antimicrobial activities of the granzymes in regards to their cytolytic and non-cytolytic activities to inhibit pathogen replication and invasion. We also discuss how reactive oxygen species contribute to the various antimicrobial mechanisms exerted by the granzymes.
Highlights
A key mechanism against intracellular pathogens, such as viruses, bacteria and parasites, is cellmediated cytotoxicity exerted by killer lymphocytes of the innate and adaptive immune systems [1, 2]
GNLY belongs to the saposin-like protein family (SAPLIP) that is characterized by a particular polypeptide motif and its affinity to a variety of lipids [15]
Though this particular field of research is only developing and further study is necessary, we think it is fair to state that the Gzms exert potent antimicrobial activities by direct proteolysis of vital microbial substrates that are crucial for their replication
Summary
A key mechanism against intracellular pathogens, such as viruses, bacteria and parasites, is cellmediated cytotoxicity exerted by killer lymphocytes of the innate and adaptive immune systems [1, 2]. When these cytotoxic immune cells recognize cells infected with intracellular pathogens, they release their cytotoxic granule contents to eliminate the target cells and the intracellular pathogen. Cytotoxicity is mediated by a group of highly homologous serine proteases, the granzymes (Gzms), that are localized in specialized lysosomes of the killer cells [3]. GNLY was found to disrupt prokaryotic (but not eukaryotic [16, 17]) membranes and to kill bacteria, parasites and fungi in vitro [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
