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.

2022年7月18日 · 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 …

Toll-like receptor (TLR) 4 belongs to the TLR family of receptors inducing pro-inflammatory responses to invading pathogens. TLR4 is activated by lipopolysaccharide (LPS, endotoxin) of Gram-negative bacteria and sequentially triggers two signaling cascades: the first one involving TIRAP and MyD88 ad …

We hypothesized that CD14 expression would naturally endow TLR4-bearing cells with the ability to promote TLR4 endocytosis, thus providing a mechanism of cell type-specific control over LPS-induced activities.

2022年5月3日 · 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.

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.

2015年6月23日 · Using alternative TLR4 agonists, or macrophages rendered tolerant to LPS, we dissociate TLR4 complex internalization from CD14 and TRIF-dependent signaling. In response to LPS, CD14 contributes to the formation of a TLR4/MD2 complex dimer that, in turn, promotes endocytosis and IRF3 activation.

2018年6月29日 · Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the …

2022年5月1日 · By using Cd14 −/− and Casp11 −/− mice strains on a Tlr4 −/− background, we have decoupled CD14’s role in caspase-11 activation from its known function in TLR4 signaling. Mechanistically, CD14 mediates caspase-11 activation by facilitating the internalization of LPS in a TLR4-independent manner.

2011年11月11日 · We identify the tyrosine kinase Syk and its downstream effector PLCγ2 as important regulators of TLR4 endocytosis and signaling. These data establish that upon microbial detection, an upstream PRR (CD14) controls the trafficking and signaling functions of a downstream PRR (TLR4).