A TLR4-independent critical role for CD14 in intracellular LPS sensing.

ABSTRACT: Intracellular lipopolysaccharide (LPS) sensing by the noncanonical inflammasome comprising caspase-4 or -11 governs antibacterial host defense. How LPS gains intracellular access in vivo is largely unknown. Here, we show that CD14-an LPS-binding protein with a well-documented role in TLR4 activation-plays a vital role in intracellular LPS sensing in vivo. By generating Cd14^-/- and Casp11^-/- mice strains on a Tlr4^-/- background, we dissociate CD14's known role in TLR4 signaling from its role in caspase-11 activation and show a TLR4-independent role for CD14 in GSDMD activation, pyroptosis, alarmin release, and the lethality driven by cytosolic LPS. Mechanistically, CD14 enables caspase-11 activation by mediating cytosolic localization of LPS in a TLR4-indepe

SUBMITTER: Vasudevan SO 

PROVIDER: S-EPMC9376664 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature