Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1258281 | ENA |
REPOSITORIES: ENA
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Project description:The postnatal microbiota-immune axis establishes lifelong homeostasis at mucosal epithelial barriers. However, whether barrier-specific physiological activities regulate this process remains ill-defined. During weaning, the oral epithelium, which is monitored by Langerhans cells (LCs), is challenged by the development of a microbial plaque and the initiation of masticatory forces capable of damaging the epithelium. We demonstrate that microbial colonization following birth facilitates the differentiation of oral LCs, setting the stage for the weaning period, where adaptive immunity develops. Despite the presence of the challenging microbial plaque, LCs mainly respond to masticatory mechanical forces, inducing adaptive immunity to maintain epithelial integrity that is also associated with bone loss. Unlike adult life, this bone loss is IL-17-independent, suggesting that the establishment and maintenance of oral mucosal homeostasis involve distinct mechanisms. Moreover, barrier-specific features play a fundamental role in this early-life process.
2023-07-17 | GSE232790 | GEO
Project description:Leber2015 - Mucosal immunity and gut
microbiome interaction during C. difficile infection
This model is described in the article:
Systems Modeling of
Interactions between Mucosal Immunity and the Gut Microbiome
during Clostridium difficile Infection.
Leber A, Viladomiu M, Hontecillas R,
Abedi V, Philipson C, Hoops S, Howard B, Bassaganya-Riera
J.
PLoS ONE 2015; 10(7): e0134849
Abstract:
Clostridium difficile infections are associated with the use
of broad-spectrum antibiotics and result in an exuberant
inflammatory response, leading to nosocomial diarrhea, colitis
and even death. To better understand the dynamics of mucosal
immunity during C. difficile infection from initiation through
expansion to resolution, we built a computational model of the
mucosal immune response to the bacterium. The model was
calibrated using data from a mouse model of C. difficile
infection. The model demonstrates a crucial role of T helper 17
(Th17) effector responses in the colonic lamina propria and
luminal commensal bacteria populations in the clearance of C.
difficile and colonic pathology, whereas regulatory T (Treg)
cells responses are associated with the recovery phase. In
addition, the production of anti-microbial peptides by inflamed
epithelial cells and activated neutrophils in response to C.
difficile infection inhibit the re-growth of beneficial
commensal bacterial species. Computational simulations suggest
that the removal of neutrophil and epithelial cell derived
anti-microbial inhibitions, separately and together, on
commensal bacterial regrowth promote recovery and minimize
colonic inflammatory pathology. Simulation results predict a
decrease in colonic inflammatory markers, such as neutrophilic
influx and Th17 cells in the colonic lamina propria, and length
of infection with accelerated commensal bacteria re-growth
through altered anti-microbial inhibition. Computational
modeling provides novel insights on the therapeutic value of
repopulating the colonic microbiome and inducing regulatory
mucosal immune responses during C. difficile infection. Thus,
modeling mucosal immunity-gut microbiota interactions has the
potential to guide the development of targeted fecal
transplantation therapies in the context of precision medicine
interventions.
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2024-09-02 | BIOMD0000000583 | BioModels
Project description:The diverse bacterial communities that colonize the gastrointestinal tract play an essential role in maintaining immune homeostasis through the production of critical metabolites such as short chain fatty acids (SCFA), and this can be disrupted by antibiotic use. However, few studies have addressed the effects of specific antibiotics longitudinally on the microbiome and immunity. We evaluated the effects of four specific antibiotics; enrofloxacin, cephalexin, paromomycin, and clindamycin; in healthy female rhesus macaques. All antibiotics disrupted the microbiome, including reduced abundances of fermentative bacteria and increased abundances of potentially pathogenic bacteria, including Enterobacteriaceae in stool, and decreased Helicobacteraceae in the colon. This was associated with decreased SCFAs, indicating altered bacterial metabolism. Importantly, antibiotic use also substantially altered local immune responses, including increased neutrophils and Th17 cells in the colon. Furthermore, we observed increased soluble-CD14 in plasma, indicating microbial translocation. These data provide a longitudinal evaluation of antibiotic-induced changes to the composition and function of colonic bacterial communities, associated with specific alterations in mucosal and systemic immunity.
2020-03-01 | GSE143729 | GEO
Project description:Innate lymphoid cells (ILCs) are critical modulators of mucosal immunity, inflammation, and tissue homeostasis, but their full spectrum of cellular states and regulatory landscapes remain elusive. Here, we use a combination of genome-wide RNA-seq, ChIP-seq and ATAC-seq to compare the transcriptional and epigenetic identity of small intestinal ILCs, identifying thousands of distinct gene profiles and regulatory elements. Single-cell RNA-seq, cytometry, and imaging analyses reveal functional compartmentalization of cytokine expression and metabolic activity within the three classical ILC subtypes, and highlight transcriptional states beyond the current canonical classification. In addition, using antibiotic intervention and germ-free mice, we characterize the effect of the microbiome on the ILC regulatory landscape, and determine the response of ILCs to microbial colonization at the single-cell level. Together, our work characterizes the spectrum of transcriptional identities of small intestinal ILCs and describes how ILCs differentially integrate signals from the microbial microenvironment to generate phenotypic and functional plasticity.
2016-08-18 | GSE85156 | GEO
Project description:Innate lymphoid cells (ILCs) are critical modulators of mucosal immunity, inflammation, and tissue homeostasis, but their full spectrum of cellular states and regulatory landscapes remain elusive. Here, we use a combination of genome-wide RNA-seq, ChIP-seq and ATAC-seq to compare the transcriptional and epigenetic identity of small intestinal ILCs, identifying thousands of distinct gene profiles and regulatory elements. Single-cell RNA-seq, cytometry, and imaging analyses reveal functional compartmentalization of cytokine expression and metabolic activity within the three classical ILC subtypes, and highlight transcriptional states beyond the current canonical classification. In addition, using antibiotic intervention and germ-free mice, we characterize the effect of the microbiome on the ILC regulatory landscape, and determine the response of ILCs to microbial colonization at the single-cell level. Together, our work characterizes the spectrum of transcriptional identities of small intestinal ILCs and describes how ILCs differentially integrate signals from the microbial microenvironment to generate phenotypic and functional plasticity.
2016-08-18 | GSE85153 | GEO
Project description:To gain insights into the in vivo function of miRNAs in the context of periodontitis, we examined the occurrence of miRNAs in healthy and diseased gingival tissues and validated their in silico-predicted targets through mRNA profiling using whole-genome microarrays in the same specimens. Eighty-six individuals with periodontitis contributed 198 gingival papillae: 158 'diseased' (bleeding-on-probing, PD > 4 mm, and AL ≥ 3 mm) and 40 'healthy' (no bleeding, PD ≤ 4 mm, and AL ≤ 2 mm). Expression of 1,205 miRNAs was assessed by microarrays, followed by selected confirmation by quantitative RT-PCR. Predicted miRNA targets were identified and tested for enrichment by Gene Set Enrichment Analysis (GSEA). Enriched gene sets were grouped in functional categories by DAVID and Ingenuity Pathway Analysis. One hundred fifty-nine miRNAs were significantly differentially expressed between healthy and diseased gingiva. Four miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917) were significantly overexpressed, and 7 (hsa-miR-1246, hsa-miR-1260, hsa-miR-141, hsa-miR-1260b, hsa-miR-203, hsa-miR-210, hsa-miR-205*) were underexpressed by > 2-fold in diseased vs. healthy gingiva. GSEA and additional filtering identified 60 enriched miRNA gene sets with target genes involved in immune/inflammatory responses and tissue homeostasis. This is the first study that concurrently examined miRNA and mRNA expression in gingival tissues and will inform mechanistic experimentation to dissect the role of miRNAs in periodontal tissue homeostasis and pathology.
2014-02-05 | GSE54710 | GEO
Project description:The impacts of individual commensal microbes on immunity and disease can differ dramatically depending on the surrounding microbial context, yet the specific bacterial combinations that dictate divergent immunological outcomes in humans remain largely undefined. We isolated a novel Allobaculum strain from an inflammatory bowel disease (IBD) patient that elicited antigen-specific mucosal and systemic antibody responses at homeostasis and exacerbated colitis in gnotobiotic mice. Using human microbiota-associated mouse models, we uncovered an inverse correlation between Allobaculum and the taxonomically-divergent immunostimulatory species Akkermansia muciniphila, which was also reflected in human cohorts. Co-colonization with Allobaculum and A. muciniphila reprogrammed the immune responses evoked by each microbe on its own, ameliorated Allobaculum-induced colitis, and blunted A. muciniphila-induced T and B cell responses. These studies thus identify a reciprocal ‘epistatic’ interaction between unique immunostimulatory human gut bacteria and establish a generalizable framework to dissect the role of microbial context in strain-specific microbial effects on human disease.
2021-12-01 | GSE179165 | GEO
Project description:Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease.
2018-09-26 | GSE95450 | GEO