A Novel Biofilm Amyloid Ligand for Caspase-11 Drives Hyperactivation in Dendritic Cells

Mintri, S.; Hu, G.; Mathur, A.; Whiteman, L. M.; Dinis, A.; Le, B.; Grando, K.; Shumba, P.; Rathinam, V. A.; Lien, E.; Tukel, C.; Fitzgerald, K. A.; Gallucci, S.

doi:10.64898/2026.09.29.755159

bioRxiv · 10.64898/2026.09.29.755159

A Novel Biofilm Amyloid Ligand for Caspase-11 Drives Hyperactivation in Dendritic Cells

Mintri, S.·Hu, G.·Mathur, A.·Whiteman, L. M.·Dinis, A.·Le, B.·Grando, K.·Shumba, P.·Rathinam, V. A.·Lien, E.·Tukel, C.·Fitzgerald, K. A.·Gallucci, S.

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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.

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Mintri, S., Hu, G., Mathur, A., Whiteman, L. M., Dinis, A., Le, B., Grando, K., Shumba, P., Rathinam, V. A., Lien, E., Tukel, C., Fitzgerald, K. A., Gallucci, S.. 2026-10-04. A Novel Biofilm Amyloid Ligand for Caspase-11 Drives Hyperactivation in Dendritic Cells. https://doi.org/10.64898/2026.09.29.755159

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