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Phenotype and Antimicrobial Activity of Th17 Cells Induced by Propionibacterium acnes Strains Associated with Healthy and Acne Skin.

ABSTRACT: Studies of the human skin microbiome suggest that Propionibacterium acnes strains may contribute differently to skin health and disease. However, the immune phenotype and functions of T helper type 17 (Th17) cells induced by healthy (PH) versus acne (PA) skin-associated P. acnes strains are currently unknown. We stimulated peripheral blood mononuclear cells from healthy donors and observed that PA strains induce higher IL-17 levels than PH strains. We next generated PH and PA strain-specific Th17 clones and show that P. acnes strains induce Th17 cells of varied phenotype and function that are stable in the presence of IL-2 and IL-23. Although PH- and PA-specific clones expressed similar levels of LL-37 and DEFB4, only PH-specific clones secreted molecules sufficient to kill P. acnes. Furthermore, electron microscopic studies showed that supernatants derived from activated PH and not PA-specific clones exhibited robust bactericidal activity against P. acnes, and complete breaches in the bacterial cell envelope were observed. This antimicrobial activity was independent of IL-26, because both natural IL-26 released by Th17 clones and rhIL-26 lacked antimicrobial potency against P. acnes. Overall, our data suggest that P. acnes strains may differentially modulate the CD4+ T-cell responses, leading to the generation of Th17 cells that may contribute to either homeostasis or acne pathogenesis.

SUBMITTER: Agak GW

PROVIDER: S-EPMC5794628 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Phenotype and Antimicrobial Activity of Th17 Cells Induced by Propionibacterium acnes Strains Associated with Healthy and Acne Skin.

Agak George W GW Kao Stephanie S Ouyang Kelsey K Qin Min M Moon David D Butt Ahsan A Kim Jenny J

The Journal of investigative dermatology 20170831 2

Studies of the human skin microbiome suggest that Propionibacterium acnes strains may contribute differently to skin health and disease. However, the immune phenotype and functions of T helper type 17 (Th17) cells induced by healthy (PH) versus acne (PA) skin-associated P. acnes strains are currently unknown. We stimulated peripheral blood mononuclear cells from healthy donors and observed that PA strains induce higher IL-17 levels than PH strains. We ...[more]

PMID: 28864077

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Project description:Emergence and potential transfer of antibiotic resistance in skin microorganisms is of current concern in medicine especially in dermatology contexts where long term treatment with antibiotics is common. Remarkably, non-antibiotic therapy in the form of isotretinoin - a non-antimicrobial retinoid is effective at reducing or eradicating the anaerobe Propionibacterium acnes which is causally involved in the complex pathogenesis of Acne vulgaris. This study measured the extent of colonization of P. acnes in patients with primary cystic or severe acne from three defined skin sites in 'non-lesion' areas before, during and after treatment with isotretinoin. Patients attending acne clinics were investigated using standardized skin sampling techniques and the recovery of anaerobic P. acnes from 56 patients comprising 24 females and 32 males (mean age 22 years, age range 15-46 years) who were given a standard course of isotretinoin (1 mg/kg/day) are reported. P. acnes cultured from the external cheek surface of patients following treatment showed a significant reduction (1-2 orders of magnitude) compared with their pre-treatment status. Interestingly, other distinct sites (nares and toe web) failed to show this reduction. In addition, high levels of antibiotic-resistant P. acnes were recorded in each patients' skin microbiota before, during and after treatment. In this study, microbial composition of the skin appears substantially altered by isotretinoin treatment, which clearly has differential antimicrobial effects on each anatomically distinct site. Our study confirmed that orally administered isotretinoin shows good efficacy in the resolution of moderate to severe acne that correlates with reductions in the number of P. acnes on the skin, including resistant isolates potentially acquired from previous treatments with antibiotics. Our study suggests that the role of tetracycline's and macrolides, which are currently first line treatments in dermatology, might be reserved for severe or life-threatening infections since current antibiotic stewardship guidelines from medical departments no longer prescribe these antibiotics for routine use.

Project description:Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne. Propionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne.

Dataset Information

Phenotype and Antimicrobial Activity of Th17 Cells Induced by Propionibacterium acnes Strains Associated with Healthy and Acne Skin.

Publications

Phenotype and Antimicrobial Activity of Th17 Cells Induced by Propionibacterium acnes Strains Associated with Healthy and Acne Skin.

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