TY - JOUR TI - Post-phagocytosis activation of NLRP3 inflammasome by two novel T6SS effectors AU - Cohen, Hadar AU - Baram, Noam AU - Fridman, Chaya Mushka AU - Edry-Botzer, Liat AU - Salomon, Dor AU - Gerlic, Motti A2 - Rothlin, Carla V VL - 11 PY - 2022 DA - 2022/09/26 SP - e82766 C1 - eLife 2022;11:e82766 DO - 10.7554/eLife.82766 UR - https://doi.org/10.7554/eLife.82766 AB - 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. KW - T6SS KW - secretion system KW - pyroptosis KW - cell death KW - gasdermin KW - caspase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -