Jun 24, 2020 · Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing …

Apr 6, 2023 · We demonstrate that GBP1 and GBP2 share the ability to form lipopolysaccharide-protein complexes, which promote caspase-4 activation. Our study provides a revised mechanistic framework for cytosolic LPS sensing and noncanonical inflammasome activation.

Apr 19, 2016 · Here we investigate the critical roles of interferon-induced GBPs in directing inflammasome subtype–specific responses and their consequences for cell-autonomous immunity to a wide variety of...

TLR4 activation by LPS was shown to induce HMGB1 release from hepatocytes followed by direct LPS binding, and the LPS translocation by induction of lysosomal rupture. Interestingly, HMGB1 has long been supposed to have high affinity to LPS and to interfere with TLR4/MD-2/CD14 signaling (138, 139).

Jul 1, 2020 · Human GBP1 (hGBP1) colocalizes with the cytosol‐resident gram‐negative bacterial pathogens Burkholderia thailandensis and S. flexneri but not gram‐positive Listeria monocytogenes (Piro et al, 2017).

Feb 18, 2022 · Scientists recently made a significant breakthrough in the recognition of pathogens via guanylate binding protein 1 (GBP1). Wandel et al. [1] in Nature Immunology described their findings where GBP1 acts as a pattern recognition receptor that directly connects to lipopolysaccharide (LPS).

GBP1 identifies gram-negative bacteria such as the enteric pathogen, Salmonella enterica serovar Typhimurium, that enter the cytoplasm of the host cell. GBP1 then quickly connects to LPS and stimulates the assembly of more GBPs in the order of GBP2, GBP3, and GBP4. Subsequently, inflammatory caspase-4 arrives at the GBP1–4 activation platform.

In addition, eight hub genes—CASP3, TLR4, NLRP3, GBP2, CASP1, CASP4, PYCARD, and GBP1—were identified by PPI network analysis using Cytoscape software. High glucose increased the protein level of GSDMD and GSDME, as critical effectors of pyroptosis, in retinal vascular endothelial cells.

We show that human GBP1 targets cytosolic Salmonella seconds after the bacteria escape from the vacuole and enter into the cytosol, and that GBP1 initiates the hierarchical recruitment of...

Jun 24, 2020 · Detection of lipopolysaccharide (LPS) is central to host defense against Gram-negative bacterial infections and to the pathogenesis of sepsis. Extracellular LPS is sensed by Toll-like receptor 4 (TLR4), which induces the production of cytokines via the MyD88 and TRIF signaling pathways 1.