Granzyme B Attenuates Bacterial Virulence by Targeting Secreted Factors.
Biological Sciences
Immune Response
Immunology
Microbiology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
27 Mar 2020
27 Mar 2020
Historique:
received:
30
09
2019
revised:
23
01
2020
accepted:
17
02
2020
pubmed:
11
3
2020
medline:
11
3
2020
entrez:
11
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32151975
pii: S2589-0042(20)30116-4
doi: 10.1016/j.isci.2020.100932
pmc: PMC7063247
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100932Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing financial interests.
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