Propionibacterium acnes Activates the NLRP3 Inflammasome in Human Sebocytes

Abstract

Propionibacterium acne and sebaceous glands are considered to have an important role in the development of acne. Although information regarding the activation of innate immunity by P. acnes in the sebaceous gland is limited, different P. acnes phylotypes and a higher prevalence of follicular P. acnes macrocolonies/biofilms in sebaceous follicles of skin biopsies from acne compared with control skin and occasionally single P. acnes clusters in single sebaceous glands have been detected. In this study, we investigated whether P. acnes activates the inflammasome in human sebaceous glands in vivo and in vitro. We found that IL-1β expression was upregulated in sebaceous glands of acne lesions. After stimulation of human sebocytes with P. acnes, the activation of caspase-1 and secretion of IL-1β were enhanced significantly. Moreover, knocking down the expression of NLRP3 abolished P. acnes-induced IL-1β production in sebocytes. The activation of the NLRP3 inflammasome by P. acnes was dependent on protease activity and reactive oxygen species generation. Finally, we found that NALP3-deficient mice display an impaired inflammatory response to P. acnes. These results suggest that human sebocytes are important immunocompetent cells that induce the NLRP3 inflammasome, and that P. acnes-induced IL-1β activation in sebaceous glands may have a role in combating skin infections and 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].…”

Autoinflammatory Skin Disease: A Review of Concepts and Applications to General Dermatology

“…Similarly, in classic acne vulgaris, aberrant innate inflammation likely plays a role specifically through interactions with P. acnes [34] . It has been shown that P. acnes activates the NLRP3 inflammasome and induces release of IL-1β from human sebocytes as well as antigen-presenting cells [36,37] . IL-1β is abundantly found in inflammatory acne lesions and along with other proinflammatory cytokines contributes to the process of follicular hyperkeratosis and inflammatory acne lesions [38] .…”