Insights into the molecular basis and mechanism of heme-triggered TLR4 signalling: The role of heme-binding motifs in TLR4 and MD2
We report the interaction of TLR4, MD2 and the TLR4-MD2 complex with heme and the consequences thereof by employing biochemical, spectroscopic, bioinformatic and physiologically relevant approaches. Heme binding occurs transiently through interaction with up to four HBMs in TLR4, two HBMs in MD2 and at least four HBMs in their complex. Functional studies highlight that mutations of individual HBMs in TLR4 preserve full receptor activation by heme, suggesting that heme interacts with TLR4 through different binding sites independently of MD2. Furthermore, we confirm and extend the major role of TLR4 for heme-mediated cytokin...
Source: Immunology - October 27, 2023 Category: Allergy & Immunology Authors: Marie-T Hopp Janine Holze Felicitas Lauber Laura Holtkamp Dhruv C Rathod Maria A Miteva Elisa B Prestes Matthias Geyer B énédicte Manoury Nicolas S Merle Lubka T Roumenina Marcelo T Bozza G ünther Weindl Diana Imhof Source Type: research
CD57 T cells associated with immunosenescence in adults living with HIV or AIDS
Immunology. 2023 Oct 25. doi: 10.1111/imm.13707. Online ahead of print.ABSTRACTDespite the advancement of human immunodeficiency virus (HIV)-related discoveries, new HIV infections still persist. With the advent of antiretroviral therapy, prognosis has migrated from acute to chronic HIV infection and inflammation, with the possibility of increased immune aging. We aimed to assess such immunosenescence by analysing CD27 and CD57 expression on the surface of T cells. This cross-sectional study was conducted between 2017 and 2018 on people living with HIV/AIDS (PLWHA) who attended an outpatient clinic of the Infectious Diseas...
Source: Immunology - October 26, 2023 Category: Allergy & Immunology Authors: Erivaldo Elias Junior Vanessa T Gubert Camila M Bonin-Jacob Marco Antonio M Puga Cl áudia G Gouveia Angela H Sichinel In ês A Tozetti Source Type: research
CD8+CD103+PD1+TIM3+ T cells in glioblastoma microenvironment correlate with prognosis
This study aimed to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumour samples were collected from 45 patients with histologically confirmed GB (WHO grade 4) and processed to obtain single-cell suspensions. Patients were assessed for the correlation of Trm phenotype with overall survival (OS) or progression-free survival (PFS) using multiparametric flow cytometry and uni/multivariate analyses. Levels of Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and m...
Source: Immunology - October 26, 2023 Category: Allergy & Immunology Authors: Giulia Romagnoli Quintino Giorgio D'Alessandris Imerio Capone Andrea Tavilla Irene Canini Caterina Lapenta Mariachiara Buccarelli Martina Giordano Valentina Tirelli Massimo Sanchez Alessandra Fragale Stefano Giannetti Rina Di Bonaventura Liverana Lauretti Source Type: research
CD57 T cells associated with immunosenescence in adults living with HIV or AIDS
Immunology. 2023 Oct 25. doi: 10.1111/imm.13707. Online ahead of print.ABSTRACTDespite the advancement of human immunodeficiency virus (HIV)-related discoveries, new HIV infections still persist. With the advent of antiretroviral therapy, prognosis has migrated from acute to chronic HIV infection and inflammation, with the possibility of increased immune aging. We aimed to assess such immunosenescence by analysing CD27 and CD57 expression on the surface of T cells. This cross-sectional study was conducted between 2017 and 2018 on people living with HIV/AIDS (PLWHA) who attended an outpatient clinic of the Infectious Diseas...
Source: Immunology - October 26, 2023 Category: Allergy & Immunology Authors: Erivaldo Elias Junior Vanessa T Gubert Camila M Bonin-Jacob Marco Antonio M Puga Cl áudia G Gouveia Angela H Sichinel In ês A Tozetti Source Type: research
CD8+CD103+PD1+TIM3+ T cells in glioblastoma microenvironment correlate with prognosis
This study aimed to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumour samples were collected from 45 patients with histologically confirmed GB (WHO grade 4) and processed to obtain single-cell suspensions. Patients were assessed for the correlation of Trm phenotype with overall survival (OS) or progression-free survival (PFS) using multiparametric flow cytometry and uni/multivariate analyses. Levels of Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and m...
Source: Immunology - October 26, 2023 Category: Allergy & Immunology Authors: Giulia Romagnoli Quintino Giorgio D'Alessandris Imerio Capone Andrea Tavilla Irene Canini Caterina Lapenta Mariachiara Buccarelli Martina Giordano Valentina Tirelli Massimo Sanchez Alessandra Fragale Stefano Giannetti Rina Di Bonaventura Liverana Lauretti Source Type: research
Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities
In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DO...
Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research
Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities
In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DO...
Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research
Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities
In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DO...
Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research
Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities
In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DO...
Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research
Structure-guided discovery of aminopeptidase ERAP1 variants capable of processing antigens with novel PC anchor specificities
In this study, we report studies on structure-guided mutational and hydrolysis kinetics, and peptide trimming assays to further examine the functional roles of this SC subsite. Most strikingly, a point mutation V737R results in a change of substrate preference from a hydrophobic to a negatively charged PC anchor residue; the latter is presumed to be a poor substrate for WT ERAP1. These studies validate the crystallographic observations that this SC subsite is directly involved in binding and recognition of the substrate PC anchor and presents a potential target to modulate MHC-restricted immunopeptidomes.PMID:37858978 | DO...
Source: Immunology - October 20, 2023 Category: Allergy & Immunology Authors: Suchita Pande Hwai-Chen Guo Source Type: research
Leishmania surface molecule lipophosphoglycan-TLR2 interaction moderates TPL2-mediated TLR2 signalling for parasite survival
Immunology. 2023 Oct 17. doi: 10.1111/imm.13702. Online ahead of print.ABSTRACTLeishmania donovani, a protozoan parasite, resides and replicates in macrophages and inflicts the potentially fatal disease visceral leishmaniasis (VL). The parasite-expressed surface lipophosphoglycan (LPG) was implicated in binding TLR2 on NK cells, but the modus operandi of its disease-promoting influence remained unknown. As TPL2, a member of the MAPK module in mammalian macrophages, was implicated in the anti-inflammatory immune response and promoting pathogen survival, we investigated the possibility of TPL2-directed LPG-TLR2 signalling in...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Soumya Kanti Gosh Divanshu Shukla Hima Mahour Sunit Kumar Srivastava Neelam Bodhale Raja Banerjee Bhaskar Saha Source Type: research
The alterations of innate immunity and enhanced severity of infections in diabetes mellitus
Immunology. 2023 Oct 17. doi: 10.1111/imm.13706. Online ahead of print.ABSTRACTDiabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysi...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Zi Zhou Hao Wang Sipin Tan Huali Zhang Yaxi Zhu Source Type: research
Leishmania surface molecule lipophosphoglycan-TLR2 interaction moderates TPL2-mediated TLR2 signalling for parasite survival
Immunology. 2023 Oct 17. doi: 10.1111/imm.13702. Online ahead of print.ABSTRACTLeishmania donovani, a protozoan parasite, resides and replicates in macrophages and inflicts the potentially fatal disease visceral leishmaniasis (VL). The parasite-expressed surface lipophosphoglycan (LPG) was implicated in binding TLR2 on NK cells, but the modus operandi of its disease-promoting influence remained unknown. As TPL2, a member of the MAPK module in mammalian macrophages, was implicated in the anti-inflammatory immune response and promoting pathogen survival, we investigated the possibility of TPL2-directed LPG-TLR2 signalling in...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Soumya Kanti Gosh Divanshu Shukla Hima Mahour Sunit Kumar Srivastava Neelam Bodhale Raja Banerjee Bhaskar Saha Source Type: research
The alterations of innate immunity and enhanced severity of infections in diabetes mellitus
Immunology. 2023 Oct 17. doi: 10.1111/imm.13706. Online ahead of print.ABSTRACTDiabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysi...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Zi Zhou Hao Wang Sipin Tan Huali Zhang Yaxi Zhu Source Type: research
Leishmania surface molecule lipophosphoglycan-TLR2 interaction moderates TPL2-mediated TLR2 signalling for parasite survival
Immunology. 2023 Oct 17. doi: 10.1111/imm.13702. Online ahead of print.ABSTRACTLeishmania donovani, a protozoan parasite, resides and replicates in macrophages and inflicts the potentially fatal disease visceral leishmaniasis (VL). The parasite-expressed surface lipophosphoglycan (LPG) was implicated in binding TLR2 on NK cells, but the modus operandi of its disease-promoting influence remained unknown. As TPL2, a member of the MAPK module in mammalian macrophages, was implicated in the anti-inflammatory immune response and promoting pathogen survival, we investigated the possibility of TPL2-directed LPG-TLR2 signalling in...
Source: Immunology - October 18, 2023 Category: Allergy & Immunology Authors: Soumya Kanti Gosh Divanshu Shukla Hima Mahour Sunit Kumar Srivastava Neelam Bodhale Raja Banerjee Bhaskar Saha Source Type: research
