Impact of NAFLD-related SNPs on the carotid atherosclerosis development; a five-year prospective observational study.

Background And Aims: The prevalence of metabolic dysfunction associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), has become a significant public health concern with an increased atherosclerotic cardiovascular disease risk. This study investigates the impact of NAFLD-related single nucleotide polymorphisms (SNPs) on carotid atherosclerosis development in a Japanese population without diabetes, dyslipidemia, and hypertension.

Methods: The prospective observational study, part of the Kyushu and Okinawa Population Study (KOPS), included 945 participants (median age 55 [47, 63]) without carotid atherosclerosis, increased alcohol intake, diabetes, dyslipidemia, hypertension, or chronic hepatitis at baseline.

A conserved human CD4+ T cell subset recognizing the mycobacterial adjuvant, trehalose monomycolate.

Mycobacterium tuberculosis causes human tuberculosis. As mycobacteria are protected by thick lipid cell wall, humans have developed immune responses against diverse mycobacterial lipids. Most of these immunostimulatory lipids are known as adjuvants acting through innate immune receptors, such as C-type lectin receptors.

Analysis of antigen specificity of Treg cell clonotypes expanded upon SARS-CoV-2 infection.

The pandemic outbreak of SARS-CoV-2 has threatened human health worldwide. Among protective immune reactions, T cell responses are diverse among individuals, which is related to the differences in severity. A T cell subset, regulatory T (Treg) cells, is crucial for limiting excessive immune responses.

Development of Ribityllumazine Analogue as Mucosal-Associated Invariant T Cell Ligands.

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells abundant in human tissues that play a significant role in defense against bacterial and viral infections and in tissue repair. MAIT cells are activated by recognizing microbial-derived small-molecule ligands presented by the MHC class I related-1 protein. Although several MAIT cell modulators have been identified in the past decade, potent and chemically stable ligands remain limited.

Analyses of the association between antibody titre and pathogenicity before and after eradication: results of the Kyushu and Okinawa population study, a retrospective observational cohort study.

Objectives: To assess the utility of antibody testing, we evaluated the correlation between the antibody titre and -associated pathogenicity and the changes in antibody titre after eradication therapy.

Design: A retrospective observational cohort study.

Setting And Participants: From 2004 to 2016, medical check-ups were performed in different regions of Japan.

Ectopic Expression of C-Type Lectin Mincle Renders Mice Susceptible to Staphylococcal Pneumonia.

Staphylococcus aureus is a prevalent pathogen in pneumonia and harbors glycolipids, which may serve as molecular patterns in Mincle (macrophage-inducible C-type lectin)-dependent pathogen recognition. We examined the role of Mincle in lung defense against S aureus in wild-type (WT), Mincle knockout (KO), and Mincle transgenic (tg) mice. Two glycolipids, glucosyl-diacylglycerol (Glc-DAG) and diglucosyl-diacylglycerol (Glc2-DAG), were purified, of which only Glc-DAG triggered Mincle reporter cell activation and professional phagocyte responses.

Regulation of MAIT cells through host-derived antigens.

Mucosal-associated invariant T (MAIT) cells are a major subset of innate-like T cells that function at the interface between innate and acquired immunity. MAIT cells recognize vitamin B2-related metabolites produced by microbes, through semi-invariant T cell receptor (TCR) and contribute to protective immunity. These foreign-derived antigens are presented by a monomorphic antigen presenting molecule, MHC class I-related molecule 1 (MR1).

Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies.

SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αβ sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing.

Innate phase production of IFN-γ by memory and effector T cells expressing early activation marker CD69 during infection with in the lungs.

is a yeast-type fungus that causes fatal meningoencephalitis in immunocompromised patients and evades phagocytic cell elimination through an escape mechanism. Memory T (Tm) cells play a central role in preventing the reactivation of this fungal pathogen. Among these cells, tissue-resident memory T (T) cells quickly respond to locally invaded pathogens.

Myeloid C-type lectin receptors in innate immune recognition.

C-type lectin receptors (CLRs) expressed by myeloid cells constitute a versatile family of receptors that play a key role in innate immune recognition. Myeloid CLRs exhibit a remarkable ability to recognize an extensive array of ligands, from carbohydrates and beyond, and encompass pattern-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and markers of altered self. These receptors, classified into distinct subgroups, play pivotal roles in immune recognition and modulation of immune responses.

Chimeric NOD2 Mincle Agonists as Vaccine Adjuvants.

There is a need for improved vaccine adjuvants to augment vaccine efficacy. One way to address this is by targeting multiple immune cell pathogen recognition receptors (PRRs) using chimeric pathogen-associated molecular patterns (PAMPs). Conjugation of the PAMPs will ensure codelivery of the immunostimulatory molecules to the same cell, enhancing adjuvant activity.

Crystal structure of the complex of CLEC12A and an antibody that interferes with binding of diverse ligands.

C-type lectin receptors (CLRs) are a family of pattern recognition receptors, which detect a broad spectrum of ligands via small carbohydrate-recognition domains (CRDs). CLEC12A is an inhibitory CLR that recognizes crystalline structures such as monosodium urate crystals. CLEC12A also recognizes mycolic acid, a major component of mycobacterial cell walls, and suppresses host immune responses.

Self-recognition through Dectin-1 exacerbates liver inflammation.

Dectin-1 is a well-characterized C-type lectin receptor involved in anti-fungal immunity through the recognition of polysaccharides; however, molecular mechanisms and outcomes initiated through self-recognition have not been fully understood. Here, we purified a water-soluble fraction from mouse liver that acts as a Dectin-1 agonist. To address the physiological relevance of this recognition, we utilized sterile liver inflammation models.

Sulfated bile acid is a host-derived ligand for MAIT cells.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize bacterial riboflavin-based metabolites as activating antigens. Although MAIT cells are found in tissues, it is unknown whether any host tissue-derived antigens exist. Here, we report that a sulfated bile acid, cholic acid 7-sulfate (CA7S), binds the nonclassical MHC class I protein MR1 and is recognized by MAIT cells.

Linkage-Editing Pseudo-Glycans: A Reductive α-Fluorovinyl--Glycosylation Strategy to Create Glycan Analogs with Altered Biological Activities.

The acetal (-glycoside) bonds of glycans and glycoconjugates are chemically and biologically vulnerable, and therefore -glycosides are of interest as more stable analogs. We hypothesized that, if the -glycoside linkage plays a vital role in glycan function, the biological activities of -glycoside analogs would vary depending on their substituents. Based on this idea, we adopted a "linkage-editing strategy" for the creation of glycan analogs (pseudo-glycans).

Fungal chitin-binding glycoprotein induces Dectin-2-mediated allergic airway inflammation synergistically with chitin.

Although chitin in fungal cell walls is associated with allergic airway inflammation, the precise mechanism underlying this association has yet to be elucidated. Here, we investigated the involvement of fungal chitin-binding protein and chitin in allergic airway inflammation. Recombinant Aspergillus fumigatus LdpA (rLdpA) expressed in Pichia pastoris was shown to be an O-linked glycoprotein containing terminal α-mannose residues recognized by the host C-type lectin receptor, Dectin-2.

Efficient lipidomic approach for the discovery of lipid ligands for immune receptors by combining LC-HRMS/MS analysis with fractionation and reporter cell assay.

C-type lectin receptors (CLRs), which are pattern recognition receptors responsible for triggering innate immune responses, recognize damaged self-components and immunostimulatory lipids from pathogenic bacteria; however, several of their ligands remain unknown. Here, we propose a new analytical platform combining liquid chromatography-high-resolution tandem mass spectrometry with microfractionation capability (LC-FRC-HRMS/MS) and a reporter cell assay for sensitive activity measurements to develop an efficient methodology for searching for lipid ligands of CLR from microbial trace samples (crude cell extracts of approximately 5 mg dry cell/mL). We also developed an in-house lipidomic library containing accurate mass and fragmentation patterns of more than 10,000 lipid molecules predicted in silico for 90 lipid subclasses and 35 acyl side chain fatty acids.

Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses.

Intranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS-CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally inefficient in inducing an antigen-specific immune response without adjuvants. Here, we developed an adjuvant-free intranasal vaccine platform that utilizes the preexisting immunity induced by previous infection or vaccination to enhance vaccine effectiveness.

The humoral and cellular immune responses following booster vaccination with SARS-CoV-2 mRNA in people living with human immunodeficiency virus.

Introduction: People living with human immunodeficiency virus (PLWH) have higher mortality rates from COVID-19 than those without HIV. Additionally, the seroconversion rate of antibodies following a second dose of SARS-CoV-2 vaccine is lower in PLWH than non-infected individuals, indicating the need for booster vaccination. Here, we evaluated the humoral and cellular immune responses to booster SARS-CoV-2 vaccination in PLWH.

Establishment of an MR1 Presentation Reporter Screening System and Identification of Phenylpropanoid Derivatives as MR1 Ligands.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are modulated by ligands presented on MHC class I-related proteins (MR1). These cells have attracted attention as potential drug targets because of their involvement in the initial response to infection and various disorders. Herein, we have established the MR1 presentation reporter assay system employing split-luciferase, which enables the efficient exploration of MR1 ligands.

Archaeal Glycerolipids Are Recognized by C-Type Lectin Receptor Mincle.

Recently, various metabolites derived from host microbes have been reported to modulate the immune system, with potential involvement in health or diseases. Archaea, prokaryotic organisms, are present in the human body, but their connection with the host is largely unknown when compared to other microorganisms such as bacteria. This study focused on unique glycerolipids from symbiotic methanogenic archaea and evaluated their activities toward an innate immune receptor.