Bacterial toxin sensing induces transient inflammasome-dependent innate immune memory that improves survival during sepsis
Abstract
Adaptive immune memory generated by bacterial toxin vaccination is well established, but whether bacterial toxins can also induce innate immune memory, or trained immunity (TI), remains unclear. Here, we show that bacterial toxins elicit TI through NLRP3 inflammasome activation both in vitro and in vivo in mice, and that this response is conserved in primary human macrophages. Stimulation with the CNF1 toxin induced an epigenetic remodeling, defining a TI-associated transcriptional signature. A targeted RNAi screen identified Bcl2a1 as a required mediator of TI, and epistasis analyses demonstrated that IL-1 signaling is essential for TI induction in macrophages. In our mouse sepsis model, toxin-induced TI enhanced host resistance and improved survival. These findings establish toxin-driven inflammasome activation as trigger of transient TI and demonstrate that this response enhance resistance during experimental bacterial sepsis.
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BibTeX
@article{torre2026bacterial,
title = {{Bacterial toxin sensing induces transient inflammasome-dependent innate immune memory that improves survival during sepsis}},
author = {Cédric Torre and Valentine Marion and Zakaryia Caillot and Ludovic Batistic and Margot Saissi and Océane Dufies and Els Verhoeyen and Grégory Michel and Patrick Munro and Céline Loubatier and Anne Doye and Paul Chaintreuil and Alexandre Gallerand and Stoyan Ivanov and Dorota Czerucka and Orane Visvikis and Bénédicte F. Py and Jessica Quintin and Laurent Boyer},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78499-5},
url = {https://www.nature.com/articles/s41467-026-78499-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bacterial toxin sensing induces transient inflammasome-dependent innate immune memory that improves survival during sepsis
AU - Cédric Torre
AU - Valentine Marion
AU - Zakaryia Caillot
AU - Ludovic Batistic
AU - Margot Saissi
AU - Océane Dufies
AU - Els Verhoeyen
AU - Grégory Michel
AU - Patrick Munro
AU - Céline Loubatier
AU - Anne Doye
AU - Paul Chaintreuil
AU - Alexandre Gallerand
AU - Stoyan Ivanov
AU - Dorota Czerucka
AU - Orane Visvikis
AU - Bénédicte F. Py
AU - Jessica Quintin
AU - Laurent Boyer
PY - 2026
DA - 2026/10/08
JO - Nature Communications
DO - 10.1038/s41467-026-78499-5
UR - https://www.nature.com/articles/s41467-026-78499-5
AB - Adaptive immune memory generated by bacterial toxin vaccination is well established, but whether bacterial toxins can also induce innate immune memory, or trained immunity (TI), remains unclear. Here, we show that bacterial toxins elicit TI through NLRP3 inflammasome activation both in vitro and in vivo in mice, and that this response is conserved in primary human macrophages. Stimulation with the CNF1 toxin induced an epigenetic remodeling, defining a TI-associated transcriptional signature. A targeted RNAi screen identified Bcl2a1 as a required mediator of TI, and epistasis analyses demonstrated that IL-1 signaling is essential for TI induction in macrophages. In our mouse sepsis model, toxin-induced TI enhanced host resistance and improved survival. These findings establish toxin-driven inflammasome activation as trigger of transient TI and demonstrate that this response enhance resistance during experimental bacterial sepsis.
SN - 2041-1723
ER -