A Novel Biofilm Amyloid Ligand for Caspase-11 Drives Hyperactivation in Dendritic Cells
- 1Laboratory of Dendritic Cell Biology, Division of Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01545
Abstract
Bacterial biofilms drive persistent infection and chronic inflammation, yet host sensing of biofilm-derived ligands remains poorly understood. Here we identify curli amyloid, an integral component of Enterobacteriaceae biofilms, as a novel activator of the non-canonical inflammasome in human and mouse dendritic cells (DCs). Curli both primes and activates the inflammasome, directly binding caspase-11 to engage NLRP3 and drive robust IL-1{beta} maturation without pyroptosis, establishing curli as a previously unrecognized trigger of DC hyperactivation. Mechanistically, this non-lytic signaling is marked by limited gasdermin D oligomerization without mitochondrial localization and NINJ1-dependent membrane rupture. Functionally, curli-hyperactivated DCs show enhanced migration to the draining lymph nodes in vivo, suggesting consequent augmented adaptive immunity. Finally, curli-containing biofilms also elicit IL-1{beta} secretion without cell death, identifying bacterial amyloid as a central driver of non-lytic inflammasome activation during immune recognition of biofilms.
Related
- Hyperactivation of the AXL-ICD/SIRT2 axis by Amyloid-β impairs astrocytic autophagic flux and exacerbates neuroinflammation
- Deficiency of NBAS causes immune dysregulation due to hyperactivation of IFN signaling.
- TRIP6 condensates constrain Hippo pathway hyperactivation under osmotic stress
- Human caspase-4 and caspase-5 assemble into non-canonical inflammasomes in response to overlapping and distinct LPS structures
- Caspase-Like Proteases as Contributors in the Functioning of Reproductive Barriers During Distant Hybridization in Solanaceae
BibTeX
@misc{mintri2026novel,
title = {{A Novel Biofilm Amyloid Ligand for Caspase-11 Drives Hyperactivation in Dendritic Cells}},
author = {S. Mintri and G. Hu and A. Mathur and L. M. Whiteman and A. Dinis and B. Le and K. Grando and P. Shumba and V. A. Rathinam and E. Lien and C. Tukel and K. A. Fitzgerald and S. Gallucci},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755159},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755159v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - A Novel Biofilm Amyloid Ligand for Caspase-11 Drives Hyperactivation in Dendritic Cells
AU - S. Mintri
AU - G. Hu
AU - A. Mathur
AU - L. M. Whiteman
AU - A. Dinis
AU - B. Le
AU - K. Grando
AU - P. Shumba
AU - V. A. Rathinam
AU - E. Lien
AU - C. Tukel
AU - K. A. Fitzgerald
AU - S. Gallucci
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755159
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755159v1
AB - Bacterial biofilms drive persistent infection and chronic inflammation, yet host sensing of biofilm-derived ligands remains poorly understood. Here we identify curli amyloid, an integral component of Enterobacteriaceae biofilms, as a novel activator of the non-canonical inflammasome in human and mouse dendritic cells (DCs). Curli both primes and activates the inflammasome, directly binding caspase-11 to engage NLRP3 and drive robust IL-1{beta} maturation without pyroptosis, establishing curli as a previously unrecognized trigger of DC hyperactivation. Mechanistically, this non-lytic signaling is marked by limited gasdermin D oligomerization without mitochondrial localization and NINJ1-dependent membrane rupture. Functionally, curli-hyperactivated DCs show enhanced migration to the draining lymph nodes in vivo, suggesting consequent augmented adaptive immunity. Finally, curli-containing biofilms also elicit IL-1{beta} secretion without cell death, identifying bacterial amyloid as a central driver of non-lytic inflammasome activation during immune recognition of biofilms.
ER -