Abstract
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-1β 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-1β secretion without cell death, identifying bacterial amyloid as a central driver of non-lytic inflammasome activation during immune recognition of biofilms.
Highlights
Amyloid curli from bacterial biofilms is a novel ligand of caspase-11 and activates non canonical inflammasome without triggering pyroptotic cell death in human and mouse dendritic cells, a process called DC hyperactivation.
Curli alone is sufficient to induce IL-1β secretion because it provides both required signals: it primes pro-IL-1β through TLR2 and TLR4 and activates the inflammasome through caspase-11.
Curli induces a limited oligomerization of mature Gasdermin-D that localizes selectively to the plasma membrane, without targeting mitochondria or undergoing NINJ1 oligomerization.
Curli-containing biofilms induce similar IL-1β secretion in viable DCs, highlighting DC hyperactivation as pivotal response during host recognition of bacterial biofilms.