Granzyme B attenuates bacterial virulence by targeting secreted factors
- López León, Diego Faculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy Unit, University of Fribourg, PER03.14, Route Albert Gockel 1, 1700 Fribourg, Switzerland
- Matthey, Patricia Faculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy Unit, University of Fribourg, PER03.14, Route Albert Gockel 1, 1700 Fribourg, Switzerland
- Fellay, Isabelle Faculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy Unit, University of Fribourg, PER03.14, Route Albert Gockel 1, 1700 Fribourg, Switzerland
- Blanchard, Marianne Faculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy Unit, University of Fribourg, PER03.14, Route Albert Gockel 1, 1700 Fribourg, Switzerland
- Martinvalet, Denis Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/B, 35121 Padova, Italy
- Mantel, Pierre-Yves Faculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy Unit, University of Fribourg, PER03.14, Route Albert Gockel 1, 1700 Fribourg, Switzerland
- Filgueira, Luis Faculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy Unit, University of Fribourg, PER03.14, Route Albert Gockel 1, 1700 Fribourg, Switzerland
- Walch, Michael Faculty of Science and Medicine, Department of Oncology, Microbiology and Immunology, Anatomy Unit, University of Fribourg, PER03.14, Route Albert Gockel 1, 1700 Fribourg, Switzerland -
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27.03.2020
Published in:
- iScience. - 2020, vol. 23, no. 3, p. 100932
English
Pathogenic bacteria secrete virulence factors that interact with the human host to establish infections. The human immune system evolved multiple mechanisms to fight bacterial invaders, including immune proteases that were demonstrated to contribute crucially to antibacterial defense. Here we show that granzyme B degrades multiple secreted virulence mediators from Listeria monocytogenes, Salmonella typhimurium, and Mycobacteria tuberculosis. Pathogenic bacteria, when infected in the presence of granzyme B or granzyme-secreting killer cells, fail to grow in human macrophages and epithelial cells owing to their crippled virulence. A granzyme B-uncleavable mutant form of the major Listeria virulence factor, listeriolysin O, rescued the virulence defect in response to granzyme treatment. Hence, we link the degradation of a single factor with the observed decrease in virulent bacteria growth. Overall, we reveal here an innate immune barrier function of granzyme B by disrupting bacterial virulence to facilitate bacteria clearance by bystander immune and non-immune cells.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 328647
- DOI 10.1016/j.isci.2020.100932
- Persistent URL
- https://folia.unifr.ch/unifr/documents/308772
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