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.

In this review, we focus on the mechanisms of the internalization and intracellular trafficking of TLR4 and CD14, and also of LPS, in immune cells and discuss how dysregulation of the endo-lysosomal compartment contributes to the development of diverse human diseases.

CD14 first captures and transports LPS to the plasma membrane localized complex of TLR4 and MD2, which signals through the TIRAP-MyD88 adaptors to activate inflammatory cytokine expression. CD14 then transports TLR4 to endosomes by a process mediated by Syk and PLCγ2, where TRAM-TRIF signaling can lead to the expression of IFNs. See also ...

2022年5月3日 · By generating Cd14 −/− mice on a Tlr4-deficient background, we reveal that CD14 plays an essential TLR4-independent role in caspase-11 activation in vivo by delivering LPS intracellularly. Thus, we demonstrate CD14 as an integral component of the noncanonical inflammasome in vivo .

2017年8月1日 · Because co-receptors influence agonist binding to TLRs, we investigated whether CD14 is required for macrophage activation induced by ArtinM.

2013年5月15日 · We assessed the potential of the TLR co-receptor CD14 as a target for therapeutics by investigating the magnitude of its influence on TLR responses. We studied the interaction of CD14 with TLR2 by conducting peptide screening and site-directed mutagenesis analysis and found TLR2 leucine-rich repeats 5, 9, 15, and 20 involved in interaction with ...

2023年12月1日 · CD14 is a co-receptor of Toll-like receptor (TLR)− 4, with a critical role in innate immune responses. CD14 recognizes bacterial lipopolysaccharides, pathogen-, and damage-associated molecular patterns, thereby facilitating inflammatory immune responses.

2022年5月3日 · 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 ...

2011年11月11日 · CD14 first captures and transports LPS to the plasma membrane localized complex of TLR4 and MD2, which signals through the TIRAP-MyD88 adaptors to activate inflammatory cytokine expression. CD14 then transports TLR4 to endosomes by a process mediated by Syk and PLCγ2, where TRAM-TRIF signaling can lead to the expression of IFNs.

In this study, we show that CD14 (cluster of differentiation 14) constitutively interacts with the MyD88-dependent TLR7 and TLR9. CD14 was necessary for TLR7- and TLR9-dependent induction of proinflammatory cytokines in vitro and for …