Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sequestration of gut pathobionts in intraluminal casts, a mechanism to avoid dysregulated T cell activation by pathobionts

ABSTRACT: T cells that express the transcription factor RORg, regulatory (Treg) or conventional (Th17), are strongly influenced by intestinal symbionts. In a genetic approach to mechanisms underlying this influence, we performed a screen for microbial genes implicated, in germfree mice monocolonized with E.coli Nissle. The loss of capsule-synthesis genes impaired clonal expansion and differentiation of intestinal RORg+ T cells. Mechanistic exploration revealed that the capsule-less mutants remained able to induce specific IgA and were highly IgA-coated. They could still trigger myeloid cells, and more effectively damaged epithelial cells in vitro. Unlike wild-type microbes, capsule-less mutants were mostly engulfed in intraluminal casts, large agglomerates composed of myeloid cells extravasated into the gut lumen. We speculate that sequestration in luminal casts of potentially harmful microbes reduces the immune system’s actual exposure, preserving host-microbe equilibrium. The variable immunostimulation by microbes charted in recent years may not solely be conditioned by triggering molecules or metabolites, but also by physical limits to immunocyte exposure.

ORGANISM(S): Mus musculus

PROVIDER: GSE211049 | GEO | 2022/09/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Composition of colonic microbes in mice deficient in intestinal Treg subsets

Project description:Regulatory T cells (Tregs) are immune cells that play a crucial role in maintaining tolerance to harmless antigens, including commensal microbes. In the intestine, Tregs can be classified into subsets based on their expression of transcription factors Helios, Rorg, Gata3 and cMaf. The exact functions of the intestinal Treg subsets and their role in maintaining tolerance to intestinal microbes is not fully understood. Here, we generated conditional knockout mice of each Treg subset and profiled the composition of their intestinal microbiota by performing 16S rRNA sequencing of stool from conditional knockouts and matched littermate controls.

2023-12-20 | GSE241887 | GEO

Commensal microbes drive the generation of large numbers of bone marrow plasma cells

Project description:The mechanisms whereby enteric pathogens and microbes induce systemic antibody responses remain obscure. In contrast to accepted models, we show that commensal microbes have a dramatic impact on the bone marrow (BM) plasma cell pool. Unlike standard vendor mice, in mice reared in our colony the majority of long-lived BM plasma cells secreted IgA antibodies. Exposing vendor mice to a unique microflora or Helicobacter sp. led to the generation of IgA-secreting BM cells, while also inducing increases in serum IgA antibodies enriched for binding to several commensal bacterial taxa. Moreover, BM IgA-secreting plasma cells exhibited a common clonal ancestry with intestinal IgA+ plasma cells, and both populations possessed unique gene expression signatures compared to other long-lived BM plasma cells. We conclude that commensal microbes overtly influence the BM plasma cell pool, and suggest that select commensal microbes can facilitate the induction of systemic humoral immunity.

2018-07-01 | GSE87091 | GEO

Impact of bacterial mono-colonization on intestinal and splenic CD4 T cells responses

Project description:Intestinal T cells responses are strongly influenced by microbes. In this study we aimed to adress how different microbes and what microbial factors influce intestinal T cells differentiation and subsequent clonal expansion. Paticularly we choose Clostridium ramosum (Cr) as a strong induced of a subest of intestinal Tregs (Rorc+), a medium inducer or Rorc+ Tregs an T1h7 Escherichia coli Nissle (EcN) and a strain that did not impact either o those cell (Pm). In addition, to study the impact of Escherichia coli Nissle (EcN) ploysaccharide K5 capsule on intestinal T cells activation, we used a EcN strain lacking the K5 capsule (kfiCD). At day 21 post-monocolonization we isolated CD4 T cells from monocolonized mice in both intestinal Lamina Propria and spleen and performed single cells RNA and TCR seq.

2022-09-27 | GSE213200 | GEO

Homeostatic, repertoire and transcriptional relationships between colon T regulatory cell subsets

Project description:Foxp3+ regulatory T cells (Tregs) in the colon are key to promoting peaceful co-existence with symbiotic microbes. Differentiated in either thymic or peripheral locations, and modulated by microbes and other cellular influencers, colonic Treg subsets have been identified through key transcription factors (TF; Helios, Rorg, Gata3, cMaf), but their inter-relationships are unclear. Here, we perform genomic analysis of colonic lamina propria Tregs with conditional KOs of each of these TFs to better understand how each TF contributes to colonic Treg identity and function.

2023-12-20 | GSE240657 | GEO

Antigen-level resolution of commensal-specific B cell responses enabled by phage-display screening and B cell tetramers

Project description:Induction of adaptive immune responses to commensal microbes is critical for intestinal homeostasis, and perturbation of these responses is associated with multiple chronic inflammatory disorders. However, the mechanisms underlying the induction and regulation of mucosal B cells targeting commensal microbes remain poorly understood, in part due to a lack of tools to identify commensal-specific B cells ex vivo. To address this, we first sought to identify immunodominant protein epitopes recognized by Segmented Filamentous Bacteria (SFB) specific serum antibodies using a whole-genome phage display screen and identified immunogenic proteins engaging IgA, IgG1 and IgG2b responses. Using these antigens, we generated B cell tetramers to identify and track SFB-specific B cell responses in the gut associated lymphoid tissue during natural and de novo colonization. We identified a compartmentalized response in B cell activation between Peyer’s patches and mesenteric lymph nodes, with a gradient of IgA, IgG1 and IgG2b isotypes along the small intestine, and selective production of IgG2b with the mesenteric lymph node chain. VDJ sequencing analyses and generation of SFB-specific monoclonal antibodies identified that somatic hypermutation drives affinity maturation to SFB derived antigens under homeostatic conditions. By combining phage display screening and B cell tetramer technologies, we now enable antigen-level based studies of immunity to intestinal microbes, which will advance our understanding of the ontogeny and function of commensal-specific B cell responses in tissue immunity, inflammation and repair.

2024-04-10 | GSE245084 | GEO

Peyer's Patch BCR repertoire analysis in mice lacking H2-Ab1 on intestinal epithelial cells

Project description:Intestinal epithelial cells (IEC) express large amounts of major histocompatibility complex II (MHCII) molecules. Despite this long-appreciated observation, the function of epithelial MHCII-mediated signaling on gut homeostasis remains enigmatic. As IECs serve as the primary cellular barrier between intestinal microbes and underlying host immune cells, we reasoned that IEC-intrinsic antigen presentation may play a role in tolerogenic responses towards the microbiota. Mice with an IEC-intrinsic defect in MHCII expression (IECΔMHCII) develop elevated T cell-dependent IgA responses, but a reduction in microbiota responsive regulatory T cells (Tregs). Despite elevated IgA levels in IECΔMHCII mice, immunoglobulin repertoires exhibit less selection and IgA has reduced reactivity to the microbiota, which is associated with increased inter-individual variability in microbiota composition. Consistent with reductions in microbiota-responsive Tregs, IECΔMHCII mice develop worsened colitis. A striking difference observed in the absence of IEC-MHCII is that while transcription of MHCII is similar, underlying mononuclear phagocytes had reduced surface MHCII. Macrophages were found to be capable of acquiring MHCII molecules from IECs, and macrophages isolated from IECΔMHCII mice had decreased capacity to stimulate Treg development. Thus, epithelial-myeloid interactions govern development of adaptive responses to microbial antigens within the gastrointestinal tract.

2021-09-09 | GSE183711 | GEO

Small intestinal immune cell distributions and transcriptomes in mice lacking H2-Ab1 on intestinal epithelial cells.

2021-09-09 | GSE183710 | GEO

CD45- EpCAM+ Intestinal Epithelial Cell Transcriptomes

2021-09-09 | GSE183709 | GEO

Distal Ileum Transcriptomes of Mice with DSS-colitis

2021-09-09 | GSE183708 | GEO

Transcriptome analysis of human colonic IgA+ plasma cell subsets and naïve B cells

Project description:Immunoglobulin A (IgA) is the most abundant antibody in the intestinal tract. Recent studies show that discrete subsets of gut human plasma cells (PCs) release IgA, which contributes to the maintenance of gut homeostasis. To better characterize the properties of these PC subsets, we performed global transcriptome analysis in naïve B cells as well as immature CD19+IgA+CD138- PCs, mature CD19+IgA+CD138+ PCs and late CD19-IgA+CD138+ PCs after their purification from human colon samples.

2020-03-29 | GSE141005 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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