Binding of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 18, 2024

Abstract SARS-CoV-2 infection triggers strong antibody response toward Nucleocapsid-Protein (NP), suggesting extracellular presence beyond its intra-virion RNA binding. Interestingly, NP was found to decorate infected and proximal uninfected cell-surfaces. Here, we propose a new mechanism through which on cells contributes COVID-19 pathogenicity. We show that binds cell-surface sulfated linear-glycosaminoglycans by spatial rearrangement of RNA-binding sites facilitated the flexible, positively charged, linker. Coating lung-derived with purified attracted anti-NP-IgG from lung fluids sera collected patients. The magnitude this immune recognition significantly elevated in moderate compared mild cases. Importantly, binding present generated clusters triggered C3b deposition classical complement pathway. Heparin analog enoxaparin outcompeted NP-binding, rescuing anti-NP IgG-mediated deposition. Our findings unveil how may exacerbate tissue damage, suggest leads for preventative therapy. Figure Highlights IgG patients’ target NP-bound resulting activation flexible linker allows both bind linear GAGs wrap around analogs prevent surface alleviate Cell-ELISA levels differ between

Language: Английский

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Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(18)

Published: Sept. 1, 2024

Abstract Introduction Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported formation of GCX promoted on cancer cells and associated tumor growth metastasis. Heparan sulfate proteoglycan glypican‐1 (GPC1) core protein overexpressed in esophageal squamous cell carcinoma (ESCC) involved development progression cells. The purpose present study analyze utility GPC1 new biomarker ralated reflects therapeutic effect prognosis ESCC. Methods We measured concentration preoperative plasma from advanced patients examined its relationships clinicopathological factors efficacy, effects extracellular were investigated. Results following clinical significantly correlated high concentration: male, size ≥30 mm, venous invasion, pT factor ≥2, pStage ≥3, residual tumor, distant metastatic recurrence. Both overall recurrence‐free survival worse group. Extracellular reflected intracellular expression. Furthermore, we recombinant human (rh)GPC1 ESCC cells, found rhGPC1 affects motility, including migration invasion. Conclusions These results demonstrated biomarker, which can be assayed less invasive blood sample‐based liquid biopsy. plays role both motility progression. Thus, useful for may potential candidate target.

Language: Английский

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Comprehensive catalogs for microbial genes and metagenome-assembled genomes of the swine lower respiratory tract microbiome identify the relationship of microbial species with lung lesions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 25, 2023

Abstract Understanding the community structure and functional capacity of lower respiratory tract microbiome is crucial for elucidating its roles in diseases. However, there are few studies about it owing to difficulty obtaining microbial samples from tract. Here we collected 745 porcine by harvesting 675 pigs, constructed a gene catalog containing 10,337,194 nonredundant genes, which only 30% could be annotated taxonomically. We obtained 397 metagenome-assembled genomes (MAGs) including 111 MAGs with high-quality. These were further clustered into 292 species-level genome bins (SGBs), among 56% SGBs unknown current databases. Combining lung lesion phenotype, found that Mycoplasma hyopneumoniae strains adhesion-related virulence factors harboring their significantly associated lesions, implying role adhesion overgrowth pathogenic M. host This study provided important resources health.

Language: Английский

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Heparan-6-O-endosulfatase 2 promotes invasiveness of head and neck squamous carcinoma cell lines in co-cultures with cancer associated fibroblasts

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 7, 2023

Abstract Local invasiveness of head and neck squamous cell carcinoma (HNSCC) is a complex phenomenon supported by interaction the cancer cells with TME. We others have shown that CAFs are component TME can promote local invasion in HNSCC other cancers. Here we report secretory enzyme Sulf-2 directly affects CAF-supported lines SCC35 Cal33 into Matrigel. The knockout (KO) differ from their wild type counterparts spheroid growths formation, Sulf-2-KO leads to decreased co-culture model CAF. Next, investigated whether fucosylated chondroitin sulfate isolated sea cucumber Holothuria Floridana (HfFucCS), activity enzyme. Our results show HfFucCS not only inhibits efficiently enzymatic but, like knockout, Matrigel co-cultured primary These findings suggest heparan 6- O -endosulfatases regulate could be therapeutically targeted inhibitory marine glycosaminoglycan. Simple Summary an early step cascade metastasis requires cooperation multiple factors types tumor microenvironment (TME). One important factor crosstalk associated fibroblasts (CAF). explore impact heparan-6- -endosulfatase 2 (Sulf-2) on CAF-assisted matrigel. knock out identified novel inhibitor that, same model, limits invasion.

Language: Английский

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The extracellular heparan sulfatase SULF2 limits myeloid IFNβ signaling and Th17 responses in inflammatory arthritis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract Heparan sulfate (HS) proteoglycans are important regulators of cellular responses to soluble mediators such as chemokines, cytokines and growth factors. We profiled changes in expression genes encoding HS core proteins, biosynthesis enzymes modifiers during macrophage polarisation, found that the most highly regulated gene was Sulf2 , an extracellular 6-O-sulfatase markedly downregulated response pro-inflammatory stimuli. then generated +/- bone marrow chimeric mice examined inflammatory antigen-induced arthritis, a model rheumatoid arthritis. Resolution inflammation impaired myeloid chimeras, with elevated joint swelling increased abundance pro-arthritic Th17 cells synovial tissue. Transcriptomic vitro analyses indicated deficiency type I interferon signaling marrow-derived macrophages, leading Th17-inducing cytokine IL-6. This establishes dynamic remodeling by limits so protects against Th17-driven pathology.

Language: Английский

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