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.

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. This hypothesis was addressed by examining the expression of CD14 in cell types that are known to express TLR4 (Hoshino et al., 1999).

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.

The cell surface antigen CD14 is primarily understood to act as a co-receptor for toll-like receptors (TLRs) to activate innate immunity responses to pathogens and tissue injury in macrophages and monocytes. However, roles for CD14 are increasingly being uncovered in disease responses in epithelial and endothelial cells.

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.

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 ...

2025年3月18日 · The LPS-TLR4 immune response is a critical mechanism in the body's defense against Gram-negative bacterial infections, yet its dysregulation can lead to severe inflammatory diseases. Lipopolysaccharide (LPS), a pivotal pathogen-associated molecular pattern (PAMP) on the surface of gram-negative bacteria, is recognized by Toll-like receptor 4 (TLR4), initiating a complex cascade of immune ...

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.

Our studies reveal that RSV F protein induced interleukin 6 (IL-6) production by monocytic cells expressing CD14 and TLR4. RSV G and N proteins induced weaker cytokine responses than F. Thus, the...