Propionibacterium acnes-Derived Extracellular Vesicles Promote Acne-Like Phenotypes in Human Epidermis

Abstract

Acne vulgaris is an inflammatory disease occurring in the pilosebaceous unit and is the most common skin condition in young people. A gram-positive bacterium, Propionibacterium acnes, has been suspected to contribute to the development of acne. Here, we report that P. acnes constitutively releases extracellular vesicles (EVs) exhibiting typical EV morphology and size. Moreover, the P. acnes-derived EVs (PEVs) can induce acne-like phenotypes in human epidermal keratinocytes and a reconstituted human skin model. PEVs significantly induced inflammatory cytokines IL-8 and GM-CSF and dysregulated epidermal differentiation by increasing proliferating keratinocytes and decreasing epidermal keratin 10 and desmocollin 1 levels. PEVs showed strong effects, evoking these responses at earlier time points compared with P. acnes extract at the same protein concentration. We verified that PEVs were internalized via clathrin-dependent endocytosis into keratinocytes and that PEV-induced cellular responses occurred via Toll-like receptor 2-dependent signal cascades. Furthermore, PEVs showed a stronger effect than keratinocytes in inducing inflammatory cytokines in myeloid cells. Collectively, our study suggests that PEVs induce acne-like phenotypes in a unique way; therefore, inhibiting the release of EVs from P. acnes or targeting PEV-mediated signaling pathways could represent an alternative method for alleviating acne occurrence and phenotypes.

Staphylococcus aureus‐derived extracellular vesicles induce monocyte recruitment by activating human dermal microvascular endothelial cells in vitro

“…Lactobacillus plantarum (APsulloc 331261) was grown in MRS broth (BD Difco, Fisher Scientific, Waltham, MA) for 24 hours at 37°C under anaerobic conditions. Each bacterial culture was harvested by centrifugation at 3000× g for 10 minutes, and gram‐positive bacterial EVs were isolated from the culture medium by ultracentrifugation at 150 000× g for 3 hours, as previously described . S. aureus extracts were prepared by sonication of the cells in phosphate‐buffered saline (PBS) on ice for 30 seconds and then centrifugation at 13 000× g for 15 minutes to harvest the membrane fractions according to a previously reported method .…”

Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process

“…43 Another communication mode was recently described: extracellular vesicles (EVs) are nowadays accepted to enable communication between host cells and bacteria, and C. acnes was recently described as a producer of EVs. [44][45][46] Moreover, Choi et al 47 recently demonstrated that C. acnes-derived EVs were capable of promoting acne-like phenotypes in human epidermis, suggesting a possible role of C. acnes EVs in acne physiopathology. These results provide new paradigms for the mechanisms that trigger skin inflammation, and they depict key data to develop future targets for innovative therapeutic approaches.…”

Extracellular Vesicles Derived from Senescent Fibroblasts Attenuate the Dermal Effect on Keratinocyte Differentiation

“…Conversely, melanocyte-derived EVs protect melanocytes and keratinocytes from UV irradiation in an autocrine or paracrine manner [8,10]. Propionibacterium acnesor Staphylococcus aureus-derived EVs are associated with acne vulgaris and atopic dermatitis, respectively [11,12]. Cellular senescence or aging is the progressive loss of the ability to maintain homeostasis and is associated with various chronic diseases.…”

“…This process is accompanied by keratinocyte proliferation and differentiation, which are the two major components of epidermal homeostasis and often disturbed in aged skin and skin disorders. The phenotypes observed in acne lesions such as hyperproliferation, diminished differentiation, and epidermal inflammation are promoted by P. acnes-derived EVs (PEVs) relative to parent cells [11]. These PEV-mediated effects on epidermal homeostasis were the opposite of those controlled by dermal fibroblast-derived EVs.…”

“…EVs reportedly regulate skin pathophysiology including development, pigmentation, and diseases such as cancer and scleroderma [7][8][9][10]. While adipose-, endothelial cell-or mesenchymal stem cell-derived EVs influence wound healing, pathogen-derived EVs are involved in the pathogenesis of skin disorders such as acne vulgaris and atopic dermatitis [7,11,12].…”