Post-phagocytosis activation of NLRP3 inflammasome by two novel T6SS effectors
- Tel Aviv University, Israel
Abstract
The type VI secretion system (T6SS) is used by bacteria to deliver toxic effectors directly into target cells. Most T6SSs mediate antibacterial activities, whereas the potential anti-eukaryotic role of T6SS remains understudied. Here, we found a Vibrio T6SS that delivers two novel effectors into mammalian host immune cells. We showed that these effectors induce a pyroptotic cell death in a phagocytosis-dependent manner; we identified the NLRP3 inflammasome as being the underlying mechanism leading to the T6SS-induced pyroptosis. Moreover, we identified a compensatory T6SS-induced pathway that is activated upon inhibition of the canonical pyroptosis pathway. Genetic analyses revealed possible horizontal spread of this T6SS and its anti-eukaryotic effectors into emerging pathogens in the marine environment. Our findings reveal novel T6SS effectors that activate the host inflammasome and possibly contribute to virulence and to the emergence of bacterial pathogens.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file
Article and author information
Author details
Funding
Israel Science Foundation (2174/22)
- Dor Salomon
- Motti Gerlic
Israel Science Foundation (920/17)
- Dor Salomon
- Motti Gerlic
Tel Aviv University Recanati
- Dor Salomon
- Motti Gerlic
Clore Israel Foundation
- Chaya Mushka Fridman
Manna Center Program, Tel Aviv University
- Chaya Mushka Fridman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Carla V Rothlin, Yale University, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of Tel Aviv University. The protocol was approved by the Committee on the Ethics of Animal Experiments of Tel Aviv University (Permit Number: 01-20-072).Experiments were performed according to the guidelines of the Institute's Animal Ethics Committees.
Version history
- Preprint posted: August 12, 2022 (view preprint)
- Received: August 17, 2022
- Accepted: August 24, 2022
- Accepted Manuscript published: September 26, 2022 (version 1)
- Version of Record published: October 7, 2022 (version 2)
Copyright
© 2022, Cohen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Post-phagocytosis activation of NLRP3 inflammasome by two novel T6SS effectors
eLife 11:e82766.
https://doi.org/10.7554/eLife.82766
