Molecular typing and functional profiling of acne-derived Cutibacterium acnes isolates reveal determinants of skin inflammation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE211279 | GEO | 2023/08/18
REPOSITORIES: GEO
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Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Experiment Overall Design: total 18 chips. 6 for acne lesion samples, 6 for normal skin samples, 6 for non-acne patient normal skin samples
2008-06-14 | E-GEOD-6475 | biostudies-arrayexpress
Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Keywords: acne lesion, normal skin
2006-12-12 | GSE6475 | GEO
Project description:Innate immune defense against deep tissue infection by Staphylococcus aureus is orchestrated by fibroblasts that become antimicrobial when triggered to differentiate into adipocytes. However, the role of this process in non-infectious human diseases is unknown. To investigate the potential role of adipogenesis by dermal fibroblasts in acne, a disorder triggered by Cutibacterium acnes (C. acnes), single-cell RNA-sequencing was performed on human acne lesions and mouse skin challenged by C. acnes. A transcriptome consistent with adipogenesis was observed within specific fibroblast subsets from human acne and mouse skin lesions infected with C. acnes. Perifollicular dermal preadipocytes in human acne and mouse skin lesions showed colocalization of PREF1, an early marker of adipogenesis, and cathelicidin (Camp), an antimicrobial peptide. This capacity of C. acnes to trigger production of cathelicidin in preadipocytes was dependent on TLR2. Treatment of wild-type mice with retinoic acid (RA) suppressed the capacity of C. acnes to form acne-like lesions, inhibited adipogenesis and enhanced cathelicidin expression in preadipocytes, but lesions were unresponsive in Camp-/- mice, despite the anti-adipogenic action of RA. Analysis of inflamed skin of acne patients after retinoid treatment also showed enhanced induction of cathelicidin, a previously unknown beneficial effect of retinoids in difficult-to-treat acne. Overall, these data provide evidence that adipogenic fibroblasts are a critical component of the pathogenesis of acne and represent a potential target for future therapy.
2022-01-16 | GSE193584 | GEO
Project description:The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-α), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-β) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy. Total of 24 chips. 12 patients : 2 biospies per patient: 1 lesional and 1 non lesional.
2014-09-25 | E-GEOD-53795 | biostudies-arrayexpress
Project description:Proprionibacterium acnes is a Gram positive bacterium found ubiquitously on human skin, where it is typically considered to assume a commensal relationship with its host. However, it is also closely associated with the skin condition acne vulgaris. More controversially, it has a postulated involvement in infections of implanted prosthetic devices and has been isolated from malignant prostate tissues. The role of P. acnes in these pathologies remains undetermined, although both bacterial and host factors are implicated. By microarray analysis, we have identified fundamental differences in the global transcriptional profiles of keratinocyte and prostate cells to P. acnes infection. Notably, P. acnes infection of the keratinocyte cell line, HaCaT, elicited a robust, but acute inflammatory response. By contrast, the inflammatory response of the prostate cell line, RWPE1, was delayed and persisted for longer times. Immunofluorescence and electron microscopy revealed higher numbers of internalized P. acnes bacteria in RWPE1 cells, which could still be detected intracellularly three weeks post infection. This contrasted with HaCaT cells, which P. acnes largely failed to invade. Moreover, P. acnes induced a delayed, sustained activation of NFM-NM-:B in RWPE1 cells, which was absent in HaCaT cells. Further characterization of the host-cell response to infection revealed that the intermediate filament protein, vimentin, was a key determinant of P. acnes invasion, persistence and inflammatory profile in RWPE1 cells. siRNA mediated knock down of vimentin in RWPE1 cells attenuated bacterial invasion and the inflammatory response to infection; similarly, overexpression of vimentin in HaCaT cells increased bacterial invasion. We conclude that vimentin-dependent host-tissue tropism, in part, determines P. acnes invasion and inflammatory capacity. This could contribute to P. acnes pathology at non-skin infection sites. Microarray experiments were performed as dual-color hybridizations. In order to compensate specific effects of the dyes and to ensure statistically relevant data analysis, a color-swap dye-reversal was performed.
2012-11-21 | E-GEOD-33731 | biostudies-arrayexpress
Project description:We performed single-cell RNA seq analysis on skin biopsies from six acne patients with a total of 32,966 cells from lesional skin and 29,202 cells from non-lesional skin using 10X Genomics. Gene expression data derived from cells in both lesional and non-lesional skin were aligned and projected onto a two-dimensional space using UMAP (Uniform Manifold Approximation and Projection). Unsupervised clustering revealed eight major clusters corresponding to seven different cell types lymphocytes, myeloid cells, keratinocytes, fibroblasts, endothelial cells, smooth muscle cells, and melanocytes.
2021-05-31 | GSE175817 | GEO
Project description:<p>Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin. In acne patients, the microbiome composition at the species level and at P. acnes strain level was more diverse than in healthy individuals, with enriched virulence-associated factors and reduced abundance of metabolic synthesis genes. Based on the abundance profiles of the metagenomic elements, we constructed a quantitative prediction model, which classified the clinical states of the host skin with high accuracy in both our study cohort (85%) and an independent sample set (86%). Our results suggest that the balance between metagenomic elements, not the mere presence of disease-associated strains, shapes the overall virulence property of the skin microbiota. This study provides new insights into the microbial mechanism of acne pathogenesis and suggests probiotic and phage therapies as potential acne treatments to modulate the skin microbiota and to maintain skin health.</p>
| phs001655 | dbGaP
Project description:Proprionibacterium acnes is a Gram positive bacterium found ubiquitously on human skin, where it is typically considered to assume a commensal relationship with its host. However, it is also closely associated with the skin condition acne vulgaris. More controversially, it has a postulated involvement in infections of implanted prosthetic devices and has been isolated from malignant prostate tissues. The role of P. acnes in these pathologies remains undetermined, although both bacterial and host factors are implicated. By microarray analysis, we have identified fundamental differences in the global transcriptional profiles of keratinocyte and prostate cells to P. acnes infection. Notably, P. acnes infection of the keratinocyte cell line, HaCaT, elicited a robust, but acute inflammatory response. By contrast, the inflammatory response of the prostate cell line, RWPE1, was delayed and persisted for longer times. Immunofluorescence and electron microscopy revealed higher numbers of internalized P. acnes bacteria in RWPE1 cells, which could still be detected intracellularly three weeks post infection. This contrasted with HaCaT cells, which P. acnes largely failed to invade. Moreover, P. acnes induced a delayed, sustained activation of NFκB in RWPE1 cells, which was absent in HaCaT cells. Further characterization of the host-cell response to infection revealed that the intermediate filament protein, vimentin, was a key determinant of P. acnes invasion, persistence and inflammatory profile in RWPE1 cells. siRNA mediated knock down of vimentin in RWPE1 cells attenuated bacterial invasion and the inflammatory response to infection; similarly, overexpression of vimentin in HaCaT cells increased bacterial invasion. We conclude that vimentin-dependent host-tissue tropism, in part, determines P. acnes invasion and inflammatory capacity. This could contribute to P. acnes pathology at non-skin infection sites.
2012-11-21 | GSE33731 | GEO
Project description:The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-α), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-β) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy.
2014-09-25 | GSE53795 | GEO
Project description:The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal, but is occasionally associated with inflammatory diseases. Recent work has indicated that evolutionary distinct lineages of P. acnes play etiologic roles in disease while others are associated with health. To shed light on the molecular basis for differential strain properties, we carried out genomic and transcriptomic analysis of distinct P. acnes strains. We sequenced the genome of the P. acnes strain 266, a type I-1a sequence type (ST) 18 strain. Comparative genome analysis of strain 266 and four other P. acnes strains revealed that overall genome plasticity is relatively low; however, a number of island-like genomic regions, encoding a variety of putative virulence-associated and fitness traits, differ between phylotypes. Comparative transcriptome analysis revealed that 225 genes of strain KPA171202 (type I-2, ST34) were differentially transcribed in strain 266 during exponential growth. 47% of these genes belong to the strain-specific gene content of strain KPA171202, indicating that strain-specific functions are utilized. Next, we studied differential expression during exponential and stationary growth phases. Genes encoding components of the energy-conserving respiratory chain as well as secreted and virulence-associated factors were transcribed during the exponential phase, while the stationary growth phase was characterized by up-regulation of genes involved in the stress response and amino acid metabolism. Taken together, our data highlight the genomic basis for strain diversity and identify, for the first time, the transcribed part of the genome, underling the important role active growth plays in the inflammatory activity of P. acnes. We argue that the disease-causing potential of different P. acnes strains is not only determined by variable genome content but also, and to a greater degree, by variable transcriptomes.
2011-07-01 | GSE26738 | GEO