A TLR4-independent critical role for CD14 in intracellular LPS sensing
Swathy O. Vasudevan, Ashley J. Russo, P. Hima Kumari, Sivapriya Kailasan Vanaja, Vijay Rathinam
Abstract
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-independent manner. Overall, our findings attribute a critical role for CD14 in noncanonical inflammasome sensing of LPS in vivo and establish-together with previous literature-CD14 as an essential proximal component of both TLR4-based extracellular and caspase-11-based intracellular LPS surveillance.
Topics & Concepts
TLR4IntracellularCD14Cell biologyChemistryComputational biologyBiologyBiochemistrySignal transductionReceptorImmune Response and InflammationInflammasome and immune disordersNeutrophil, Myeloperoxidase and Oxidative Mechanisms