Propionibacterium acnes Induces IL-1β Secretion via the NLRP3 Inflammasome in Human Monocytes

Abstract

Propionibacterium acnes induction of inflammatory responses is a major etiologic factor contributing to the pathogenesis of acne vulgaris. In particular, the IL-1 family of cytokines plays a critical role in both initiation of acne lesions and in the inflammatory response in acne. In this study, we demonstrated that human monocytes respond to P. acnes and secrete mature IL-1β partially via NLRP3 mediated pathway. When monocytes were stimulated with live P. acnes, caspase-1 and caspase-5 gene expression was upregulated; however, IL-1β secretion required only caspase-1 activity. P. acnes induced key inflammasome genes including NLRP1 and NLPR3. Moreover, silencing of NLRP3, but not NLRP1, expression by siRNA attenuated P. acnes-induced IL-1β secretion. The mechanism of P. acnes-induced NLRP3 activation and subsequent IL-1β secretion was found to involve potassium efflux. Finally, in acne lesions, mature caspase-1 and NLRP3 were detected around the pilosebaceous follicles and co-localized with tissue macrophages. Taken together, our results indicate that P. acnes triggers a key inflammatory mediator, IL-1β, via NLRP3 and caspase-1 activation, suggesting a role for inflammasome-mediated inflammation in acne pathogenesis.

PASS Syndrome: An IL-1-Driven Autoinflammatory Disease

“…For example, acne vulgaris, which has an IL-1-driven autoinflammatory component as Propionibacterium acnes can directly trigger the assembly of the NLRP3 inflammasome [10,11,12], can be associated with spondylarthropathies [2]. The SAPHO syndrome describes a spectrum of inflammatory bone disorders including spondylarthropathies and skin manifestations including acne, pyoderma gangrenosum and hidradenitis suppurativa.…”

Interactions between host factors and the skin microbiome

“…Recently, a number of independent reports confirmed the ability of P. acnes to upregulate the production of IL-1β through the activation of the NLRP3 inflammasome [88-90]. Higher expression levels of NLRP3 and caspase-1 were observed in the areas surrounding acne lesions and both markers co-localized with infiltrating tissue macrophages [88, 90].…”

“…Higher expression levels of NLRP3 and caspase-1 were observed in the areas surrounding acne lesions and both markers co-localized with infiltrating tissue macrophages [88, 90]. Mice challenged with P. acnes also showed increased expression of caspase-1 and IL-1β, while NLRP3 knockout mice displayed a significant decrease in these inflammatory markers [89, 90].…”

“…Mice challenged with P. acnes also showed increased expression of caspase-1 and IL-1β, while NLRP3 knockout mice displayed a significant decrease in these inflammatory markers [89, 90]. In sebocytes, this activity was dependent upon reactive oxygen species and P. acnes protease activity, while monocytes required bacterial uptake, potassium efflux, and reactive oxygen species [88-90]. This information, coupled with studies showing increased expression of TLR-2 on acne-localized macrophages [83], suggests a mechanism by which monocytes are recruited to early acne lesions, and then activated by P. acnes to induce a more robust inflammatory response.…”

Acne Pathogenesis: History of Concepts

“…Qin et al [268] provided evidence of the role of P. acnes in the inflammatory phase of the acne sequence by triggering the activation of the NLRP3 inflammasome - a cytoplasmic molecular complex that initiates inflammation upon sensing pathogen - and finally enhancing IL-1β secretion, therefore leading to new expectations in acne treatment [269]. However, despite these new ways of understanding, ‘how and if P. acnes influences the development and perpetuation of acne lesions remains unclear at this stage' [270].…”