Fucosylated haptoglobin drives inflammation via Mincle in sepsis: an observational study
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PROVIDER: PRJNA1128610 | ENA |
REPOSITORIES: ENA
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Project description:Fucosylated haptoglobin drives inflammation via Mincle in sepsis: an observational study
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Project description:Fucosylated haptoglobin drives inflammation via Mincle in sepsis: an observational study [scRNAseq_Sepsis]
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Project description:Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis patients (SPs) remains limited. Our study reveals elevated levels of terminal fucosylation at Asn207 and Asn211 of Hp in SP plasma, along with heightened inflammatory responses, compared to healthy controls (trial registration NCT05911711). Fucosylated (Fu)-Hp purified from SPs upregulates inflammatory cytokines and chemokines, along with NLRP3 inflammasome activation. Single-cell RNA sequencing identifies a distinct macrophage-like cell population with increased expressions of inflammatory mediators and FUT4 in response to Fu-Hp. Additionally, Mincle, a C-type lectin receptor, interacts with Fu-Hp to amplify the inflammatory responses and signaling. Moreover, the Hp fucosylation (AAL) level significantly correlates with the levels of inflammatory cytokines in sepsis patients, suggesting that Fu-Hp is clinically relevant. Finally, Fu-Hp treatment significantly enhances the levels of inflammatory cytokines in the plasma and various tissues of mice. Together, our findings reveal a previously unrecognized role of Fu-Hp, derived from sepsis patients, in driving inflammation, and suggest that targeting Fu-Hp could serve as a promising intervention for combating sepsis.
2025-01-15 | GSE286141 | GEO
Project description:Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis patients (SPs) remains limited. Our study reveals elevated levels of terminal fucosylation at Asn207 and Asn211 of Hp in SP plasma, along with heightened inflammatory responses, compared to healthy controls (trial registration NCT05911711). Fucosylated (Fu)-Hp purified from SPs upregulates inflammatory cytokines and chemokines, along with NLRP3 inflammasome activation. Single-cell RNA sequencing identifies a distinct macrophage-like cell population with increased expressions of inflammatory mediators and FUT4 in response to Fu-Hp. Additionally, Mincle, a C-type lectin receptor, interacts with Fu-Hp to amplify the inflammatory responses and signaling. Moreover, the Hp fucosylation (AAL) level significantly correlates with the levels of inflammatory cytokines in sepsis patients, suggesting that Fu-Hp is clinically relevant. Finally, Fu-Hp treatment significantly enhances the levels of inflammatory cytokines in the plasma and various tissues of mice. Together, our findings reveal a previously unrecognized role of Fu-Hp, derived from sepsis patients, in driving inflammation, and suggest that targeting Fu-Hp could serve as a promising intervention for combating sepsis.
2025-01-15 | GSE270838 | GEO
Project description:Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis patients (SPs) remains limited. Our study reveals elevated levels of terminal fucosylation at Asn207 and Asn211 of Hp in SP plasma, along with heightened inflammatory responses, compared to healthy controls (trial registration NCT05911711). Fucosylated (Fu)-Hp purified from SPs upregulates inflammatory cytokines and chemokines, along with NLRP3 inflammasome activation. Single-cell RNA sequencing identifies a distinct macrophage-like cell population with increased expressions of inflammatory mediators and FUT4 in response to Fu-Hp. Additionally, Mincle, a C-type lectin receptor, interacts with Fu-Hp to amplify the inflammatory responses and signaling. Moreover, the Hp fucosylation (AAL) level significantly correlates with the levels of inflammatory cytokines in sepsis patients, suggesting that Fu-Hp is clinically relevant. Finally, Fu-Hp treatment significantly enhances the levels of inflammatory cytokines in the plasma and various tissues of mice. Together, our findings reveal a previously unrecognized role of Fu-Hp, derived from sepsis patients, in driving inflammation, and suggest that targeting Fu-Hp could serve as a promising intervention for combating sepsis.
2025-01-15 | GSE286922 | GEO
Project description:Fucosylated haptoglobin drives inflammation via Mincle in sepsis: an observational study [scRNAseq_Fu-Hp]
| PRJNA1210551 | ENA
Project description:Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis patients (SPs) remains limited. Our study reveals elevated levels of terminal fucosylation at Asn207 and Asn211 of Hp in SP plasma, along with heightened inflammatory responses, compared to healthy controls (trial registration NCT05911711). Fucosylated (Fu)-Hp purified from SPs upregulates inflammatory cytokines and chemokines, along with NLRP3 inflammasome activation. Single-cell RNA sequencing identifies a distinct macrophage-like cell population with increased expressions of inflammatory mediators and FUT4 in response to Fu-Hp. Additionally, Mincle, a C-type lectin receptor, interacts with Fu-Hp to amplify the inflammatory responses and signaling. Moreover, the Hp fucosylation (AAL) level significantly correlates with the levels of inflammatory cytokines in sepsis patients, suggesting that Fu-Hp is clinically relevant. Finally, Fu-Hp treatment significantly enhances the levels of inflammatory cytokines in the plasma and various tissues of mice. Together, our findings reveal a previously unrecognized role of Fu-Hp, derived from sepsis patients, in driving inflammation, and suggest that targeting Fu-Hp could serve as a promising intervention for combating sepsis.
2025-01-15 | GSE286921 | GEO
Project description:Cholera toxin (CT) is the etiological agent of cholera. Here we report that multiple classes of fucosylated glycoconjugates function in CT binding and intoxication of intestinal epithelial cells. In Colo205 cells, knockout of B3GNT5, the enzyme required for synthesis of lacto- and neolacto-series glycosphingolipids (GSLs), reduces CT binding but sensitizes cells to intoxication. Overexpressing B3GNT5 to generate more fucosylated GSLs confers protection against intoxication, indicating that fucosylated GSLs act as decoy receptors for CT. Knockout (KO) of B3GALT5 causes increased production of fucosylated O-linked and N-linked glycoproteins, and leads to increased CT binding and intoxication. Knockout of B3GNT5 in B3GALT5 KO cells eliminates production of fucosylated GSLs but increases intoxication, identifying fucosylated glycoproteins as functional receptors for CT. These findings provide insight into molecular determinants regulating CT sensitivity of host cells.
2024-08-31 | GSE242156 | GEO
Project description:This prospective observational study conducted at Osaka University Graduate School of Medicine aimed to compare host responses in sepsis and COVID-19 patients by analyzing mRNA and miRNA profiles. They included 22 sepsis patients, 35 COVID-19 patients, and 15 healthy subjects. Sepsis was diagnosed using Sepsis-3 criteria, while COVID-19 was confirmed through SARS-CoV-2 RT-PCR testing and chest CT scans for pneumonia assessment. For RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in sepsis patients. Numbers of genes showing upregulated:downregulated gene expression (false discovery rate <0.05, |log2 fold change| >1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in COVID-19 patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated:downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. Sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to COVID-19 patients, indicating a dynamic change in gene expression and pathway activation in sepsis.
2024-08-28 | GSE243218 | GEO
Project description:This prospective observational study conducted at Osaka University Graduate School of Medicine aimed to compare host responses in sepsis and COVID-19 patients by analyzing mRNA and miRNA profiles. They included 22 sepsis patients, 35 COVID-19 patients, and 15 healthy subjects. Sepsis was diagnosed using Sepsis-3 criteria, while COVID-19 was confirmed through SARS-CoV-2 RT-PCR testing and chest CT scans for pneumonia assessment. For RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in sepsis patients. Numbers of genes showing upregulated:downregulated gene expression (false discovery rate <0.05, |log2 fold change| >1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in COVID-19 patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated:downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. Sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to COVID-19 patients, indicating a dynamic change in gene expression and pathway activation in sepsis.
2024-08-28 | GSE243217 | GEO