Contextual control of skin immunity and inflammation by <i>Corynebacterium</i>

Ridaura, Vanessa K.; Bouladoux, Nicolas; Claesen, Jan; Chen, Y. Erin; Byrd, Allyson L.; Constantinides, Michael G.; Merrill, Eric Dean; Tamoutounour, Samira; Fischbach, Michael A.; Belkaid, Yasmine

doi:10.1084/jem.20171079

Cited by 164 publications

(155 citation statements)

References 43 publications

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“…Notably, this correlation is supported by experimental observations that TCRgd + T cells are capable of recognizing microbial lipid antigens, including mycolic acids (Ridaura et al, 2018). Together these results demonstrate that certain concepts established in animal models can be validated using human subject data.…”

Section: Bacterial Species and Microbial Pathways Are Associated Withsupporting

confidence: 52%

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

Byrd¹,

Liu

Fujimura³

et al. 2020

Preprint

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Analysis of 1,363 deeply sequenced gut microbiome samples from 946 healthy donors of the Milieu Intérieur cohort provides new opportunities to discover how the gut microbiome is associated with host factors and lifestyle parameters. Using a genomebased taxonomy to achieve higher resolution analysis, we found an enrichment of Prevotella species in males, and that bacterial profiles are dynamic across five decades of life (20-69), with Bacteroidota species consistently increased with age while Actinobacteriota species, including Bifidobacterium, decreased. Longitudinal sampling revealed short-term stability exceeds inter-individual differences; however, the degree of stability was variable between donors and influenced by their baseline community composition. We then integrated the microbiome results with systemic immunophenotypes to show that host/microbe associations discovered in animal models, such as T regulatory cells and short chain fatty acids, could be validated in human data.These results will enable personalized medicine approaches for microbial therapeutics and biomarkers. ¶ unless otherwise indicated, partners are located at

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Section: Bacterial Species and Microbial Pathways Are Associated Withsupporting

confidence: 52%

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

Byrd¹,

Liu

Fujimura³

et al. 2020

Preprint

Self Cite

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“…C. j . is an opportunistic human pathogen reported to induce inflammatory cytokines, such as IL17a . S. e .…”

Section: Resultsmentioning

confidence: 79%

“…3.2 | Differential effects of C. t., C. j., and S. e. on mRNA expression in HEKs and SCC cells C. j. is an opportunistic human pathogen reported to induce inflammatory cytokines, such as IL17a. 12,21,39 S. e. is a cutaneous commensal in humans, which can become an opportunistic pathogen, accounting for ∼22% of systemic infections in intensive care patients in the United States. 40 We infected HEKs and SCC cells with C. t., C. j., or S. e. for 6 hours and quantified the mRNA expression of the genes that showed significant induction by treatment with C. t. or TNF in the experiments of Figure 1.…”

Section: Upregulates the Mrna And Protein Levels Of Inflammatory Medimentioning

confidence: 99%

“…For example, colonization of the skin by Propionibacterium acnes is causally related to facial acne . In turn, the inflammatory and metabolic status of the host regulate the functional impact of microbes . Furthermore, host genetic factors are determinants of a skin microbiota predisposing to skin health or pathology; for example, the skin of patients with atopic dermatitis, a genetic disease related etiologically to mutations of the filaggrin (FLG) gene, demonstrates increased colonization with Staphylococcus aureus and Staphylococcus epidermidis ( S. e .)…”

Section: Introductionmentioning

confidence: 99%

“…10,11 In turn, the inflammatory and metabolic status of the host regulate the functional impact of microbes. 12 Furthermore, host genetic factors are determinants of a skin microbiota predisposing to skin health or pathology; for example, the skin of patients with atopic dermatitis, a genetic disease related etiologically to mutations of the filaggrin (FLG) gene, demonstrates increased colonization with Staphylococcus aureus and Staphylococcus epidermidis (S. e.). 13,14 In healthy skin, commensals are unlikely to cause skin inflammation in the absence of a compromised epidermal barrier.…”

Section: Introductionmentioning

confidence: 99%

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Corynebacterium tuberculostearicum, a human skin colonizer, induces the canonical nuclear factor‐κB inflammatory signaling pathway in human skin cells

Altonsy

Kurwa

Lauzon

et al. 2020

Immunity Inflam & Disease

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Introduction Corynebacterium tuberculostearicum (C. t.) is a ubiquitous bacterium that colonizes human skin. In contrast to other members of the genus Corynebacterium, such as toxigenic Corynebacterium diphtheriae or the opportunistic pathogen Corynebacterium jeikeium, several studies suggest that C. t. may play a role in skin health and disease. However, the mechanisms underlying these effects remain poorly understood. Methods To investigate whether C. t. induces inflammatory pathways in primary human epidermal keratinocytes (HEKs) and human cutaneous squamous carcinoma cells (SCCs), cell culture, reverse transcription‐polymerase chain reaction (PCR), enzyme‐linked immunosorbent assay, immunofluorescence microscopy, Western blot, chromatin immunoprecipitation‐PCR, small interfering RNA knockdown and luciferase reporter expression system were used. Results Herein, we demonstrate that C. t. upregulates the messenger RNA (mRNA) and protein levels of inflammatory mediators in two human skin cell lines, HEKs and SCCs. We further show activation of the canonical nuclear factor‐κB (NF‐κB) pathway in response to C. t. infection, including phosphorylation of the inhibitor of κB (IκB), the nuclear translocation of NF‐κB subunit (NF‐κB‐P65) and the recruitment of NF‐κB‐P65 and RNA polymerase to the NF‐κB response elements at the promoter region of the inflammatory genes. Lastly, the data confirm that C. t.‐induced tumor necrosis factor mRNA expression in HEKs is toll‐like receptor 2 (TLR2) dependent. Conclusion Our results offer a mechanistic model for C. t.‐induced inflammation in human keratinocytes via TLR2 and activation of IκB kinase and downstream signaling through the canonical NF‐κB pathway. Relevance to chronic inflammatory diseases of the skin and cutaneous oncology is discussed.

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Genetic Disorders of Adipose Tissue

Millington

2024

Rook's Textbook of Dermatology

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Subcutaneous fat consists of white, brown and beige adipose tissue, with diverse metabolic, thermogenic, paracrine, endocrine and immune functions. Disorders of adipose tissue can be divided principally into: disorders of distribution of fat, the lipodystrophies, lipoedema and fibroadipose hyperplasia, disorders of excessive generalised accumulation of fat (in other words obesity), tumours and inflammation (such as panniculitis). There is increasing evidence of a hereditary component in the pathogenesis of all of these conditions.

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Contextual control of skin immunity and inflammation by Corynebacterium

Abstract: Belkaid et al. show that Corynebacterium, a dominant skin microbe, promotes activation of γδ T cells in a mycolic acid–dependent manner without altering skin homeostasis. Such effect promotes inflammation in the context of high-fat-diet and psoriasis-like settings.

Cited by 164 publications

References 43 publications

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

Corynebacterium tuberculostearicum, a human skin colonizer, induces the canonical nuclear factor‐κB inflammatory signaling pathway in human skin cells

Genetic Disorders of Adipose Tissue

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