Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bacterial membrane phosphatidylglycerols activate a population of human CD1a-restricted t cells

ABSTRACT: Expressed on epidermal Langerhans cells, CD1a presents a range of self-lipid antigens found within the skin. However, the extent to which CD1a presents microbial ligands from skin bacteria is unclear. Here, we identified CD1a-dependent T cell responses to phosphatidylglycerol (PG), a ubiquitous bacterial membrane phospholipid, as well as to lysyl phosphatidylglycerol (lysylPG), a modified PG, present in the many gram positive bacteria, and highly abundant in Staphylococcus aureus. Specifically, PG and lysylPG together constitute the vast majority of the structural membrane lipids in Staphylococcus aureus. The crystal structure of the CD1a-lysylPG complex showed that the acyl chains were buried within the A′- and F′-pockets of CD1a, while the lysine-modified phosphoglycerol headgroup protruded from the F′-portal and was available for T cell receptor contact. Using lysylPG-loaded CD1a tetramers, we identified T cells in peripheral blood and in skin that respond to this lipid in a dose dependent manner. Tetramer+ CD4+ T cell lines secreted Th2 cytokines in response to lysylPG as well as to co-cultures of CD1a+ dendritic cells and Staphylococcus aureus. The expansion of CD4+ CD1a-lysylPG tetramer+ T cells in atopic dermatitis patients, indicates a response to a lipid made by bacteria associated with atopic dermatitis, and provide a link supporting involvement of PG-based lipid-specific T cells in the pathogenesis of dermatitis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186459 | GEO | 2022/12/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

GNPS - Staphylococcus aureus SA113 - Mice atopic dermatitis experiments

Project description:GNPS - Staphylococcus aureus SA113 - Mice atopic dermatitis experiments and culture of SA113

2019-03-16 | MSV000083584 | GNPS

Next Generation Sequencing Facilitates Quantitative Analysis of Stat3f/f K5cre Skin Keratinocytes Transcriptomes

Project description:Atopic dermatitis (AD) is the most common inflammatory skin disease. Stat3 mutation is a major cause of hyper IgE syndrome (HIES), which consistently represent AD like eczematous dermatitis. Based on multi-dimensional transcriptome analysis in pre- and post-flares skin, dermatitis phenotype was controlled by sequential two steps of Stat3 deficiency and environmental pathogenic stimuli. The Stat3 deficiency determined the barrier integrity that lowered threshold of inflammation, but this step was not sufficient to form pathogenicity. Transcriptome data indicated that emergence of dermatitis phenotype need to trigger robust activation of NFB pathway and TH2 cells. Continuous colonization of Staphylococcus aureus was an environmental stimulus to lower the activation threshold of TH2 inflammation in the skin.

2021-10-12 | GSE185340 | GEO

Host cellular and immune responses in models of inflammatory skin conditions

Project description:Skin colonisation of varied communities of commensal microorganisms, such as Staphylococcus aureus (SA), Staphylococcus epidermidis (SE) and Staphylococcus capitis (SC) form the microbiome; a necessity for healthy skin. The skin changes characteristic of atopic dermatitis, a common inflammatory skin disease, have been shown to provide a favourable niche for SA colonisation. We utilised a reconstructed human epidermal (RHE) model recapitulating the stratified anatomy of the epidermis on which to test host responses to bacterial colonisation. SA proliferation was significantly inhibited in contrast to that seen with SE at both high and low colonisation loads after 24 hours. These data strongly suggest species specific regulation of staphylococcal growth, which is partially mediated by interaction with the epidermis.

2023-01-16 | GSE192454 | GEO

Pseudomonas-derived Ceramidase Induces Production of Inflammatory Mediators from Human Keratinocytes via Sphingosine-1-Phosphate

Project description:A Pseudomonas aeruginosa-derived neutral ceramidase (PaCDase) isolated from a patient with atopic dermatitis was shown to effectively degrade ceramide in the presence of Staphylococcus aureus-derived lipids or neutral detergents. To understand the effect of ceramide metabolites on the functions of differentiating keratinocytes, we have conducted genes expressions analysis from PaCDase-, sphingosine-1-phosphate (S1P)-treated or untreated three-dimensionally cultured human primary keratinocytes, which form a stratum corneum, in the presence of Triton X-100 using high resolution DNA microarray.

2014-12-25 | GSE53670 | GEO

Polarizing Cytokines and Staphylococcus aureus Cooperatively Induce Atopic Dermatitis-Like Transcriptomes

Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease with a TH2 immune polarity and is often colonized with Staphylococcus aureus. Despite recent advances in understanding Staphylococcus species infection and the impact of polar TH cytokines on the skin, the interactions between these factors in AD pathology are poorly understood. Methods: AD-related key immune biomarkers were measured by quantitative real-time PCR in human keratinocytes exposed heat-killed S. epidermidis or S. aureus with/without polar T-cell derived cytokines such as IFN-γ (TH1), IL-4/IL-13 (TH2), and IL-22 (TH22). Further analysis was performed by RNA-sequencing to define broader responses in both Staphylococcus species and polar cytokines. The similarity of gene expression patterns in AD skin lesions and stimulated keratinocytes was evaluated by gene-set variation analysis (GSVA). Results: Gene expression analysis exhibited distinct immune responses in keratinocytes depending on individual bacterial or polar cytokine exposure. Besides, numerous genes were synergistically upregulated by the combination exposure of bacteria and polar TH cytokines. Moreover, GSVA revealed that combined exposure of S. aureus and IL-4 + IL-13 exhibited significantly higher correlations with a genomic signature of AD skin lesions than their single exposure or combinations of other polar TH cytokines. Conclusions: Our findings provide novel insights into AD-related transcriptional activation and illustrate a potentially novel pathogenic function of S. aureus and IL-4/IL-13 interactions in AD.

2021-12-31 | GSE173902 | GEO

Staphylococcus aureus

Project description:Staphylococcus aureus genome sequencing and assembly: atopic dermatitis

| PRJNA511152 | ENA

Local and systemic changes in lipid profile as potential biomarkers for canine atopic dermatitis.

Project description:Lipids play a critical role in the skin as components of the epidermal barrier and as sig-naling molecules. Atopic dermatitis in dogs is associated with changes in the lipid composition of the skin, but whether these precede the onset of dermatitis or occur secondary to the dermatitis is unclear. We applied rapid lipid profiling mass spectrometry methods to skin and blood samples of dogs and determined changes following systemic treatment. Thirty control dogs and 30 atopic dogs with mild to moderate dermatitis were enrolled. Marked differences in lipid profiles were observed between control, nonlesional and lesional skin of dogs. Additionally, there were significant altera-tions in the lipid composition of the blood samples indicating systemic changes in lipid metabolism. Treatment with oclacitinib or lokivetmab resulted in a significant decrease of the disease clinical severity associated with changes in skin and blood lipids. A set of lipid features of the skin were selected as biomarkers that classified samples as control or atopic dermatitis with 95% accuracy, whereas blood lipids discriminated between control and atopic dogs with 82% accuracy. These data suggest that atopic dermatitis is a systemic disease and support the use of rapid lipid profiling to identify novel biomarkers.

2021-07-16 | MSV000087837 | MassIVE

The antimicrobial peptide-sensing system aps of Staphylococcus aureus

Project description:Staphylococcus aureus is a leading cause of hospital-associated infections. In addition, highly virulent strains of methicillin-resistant S. aureus (MRSA) are currently spreading outside health care settings. Survival in the human host is largely defined by the ability of S. aureus to resist mechanisms of innate host defense, of which antimicrobial peptides form a key part especially on epithelia and in neutrophil phagosomes. Here we demonstrate that the antimicrobial-peptide sensing system aps of the standard community-associated MRSA strain MW2 controls resistance to cationic antimicrobial peptides. The core of aps-controlled resistance mechanisms comprised the D-alanylation of teichoic acids (dlt operon), the incorporation of cationic lysyl-phosphatidylglycerol (L-PG) in the bacterial membrane (mprF), and the vraF/vraG putative antimicrobial peptide transporter. Further, the observed increased production of L-PG under the influence of cationic antimicrobial peptides was accompanied by the up-regulation of lysine biosynthesis. In noticeable difference to the aps system of S. epidermidis, only selected antimicrobial peptides strongly induced the aps response. Heterologous complementation with the S. epidermidis apsS gene indicated that this is likely caused by differences in the short extracellular loop of ApsS that interacts with the inducing antimicrobial peptide. Our study shows that the antimicrobial peptide sensor system aps is functional in the important human pathogen S. aureus, significant interspecies differences exist in the induction of the aps gene regulatory response, and aps inducibility is clearly distinguishable from effectiveness towards a given antimicrobial peptide. Keywords: Wild type control vs treated vs mutant Wild type untreated in triplicate is compared to wild type treated in triplicate along with three mutants in triplicate with and without treatment of indolicidin, totalling 30 samples

2008-04-06 | E-GEOD-8400 | biostudies-arrayexpress

Skin Microbiome in Disease States: Atopic Dermatitis and Immunodeficiency

Project description:<p>The NIH Intramural Skin Microbiome Consortium (NISMC) is a collaboration of investigators with primary expertise in genomics, bioinformatics, large-scale DNA sequencing, dermatology, immunology, allergy, infectious disease, and clinical microbiology. Atopic dermatitis (AD, "eczema") is a chronic relapsing skin disorder that affects ~15% of U.S. children and is associated with $1 billion of medical costs annually. AD is characterized by dry, itchy skin, infiltrated with immune cells. Colonization by Staphylococcus aureus (S. aureus) is ten-fold more common in AD patients and is associated with disease flares. We hypothesize that, in addition to S. aureus, AD may also be associated with additional novel microbes and/or selective shifts of commensal microbes that are relevant to disease progression. The NISMC seeks to define the microbiota that resides in and on the skin and nares of three patient groups, all of whom have eczematous lesions and are currently seen at the NIH Clinical Center: (1) AD patients; (2) Wiskott-Aldrich syndrome (WAS) patients; and (3) Hyper IgE syndrome (HIES) syndrome patients. Examination of the microbiome of patients with WAS or HIES syndromes, both rare immunodeficiencies, will advance our understanding of how an individual's immune system shapes their cutaneous microbial community. We are performing a prospective longitudinal study that follows these groups of patient thorough the cycles of eczema flares, ascertaining clinical data and samples at each stage.</p>

| phs000266 | dbGaP

Project description:On-person evolution of Staphylococcus aureus during atopic dermatitis

| PRJNA715375 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data