IL-1β Drives Inflammatory Responses to Propionibacterium acnes In Vitro and In Vivo

Abstract

Acne vulgaris is potentially a severe skin disease associated with colonization of the pilo-sebaceous unit by the commensal bacterium Propionibacterium acnes and inflammation. P. acnes is considered to contribute to inflammation in acne, but the pathways involved are unclear. Here we reveal a mechanism that regulates inflammatory responses to P. acnes. We show that IL-1β mRNA and the active processed form of IL-1β are abundant in inflammatory acne lesions. Moreover, we identify P. acnes as a trigger of monocyte-macrophage NLRP3-inflammasome activation, IL-1β processing and secretion that is dependent on phagocytosis, lysosomal destabilization, reactive oxygen species, and cellular K+ efflux. In mice, inflammation induced by P. acnes is critically dependent on IL-1β and the NLRP3 inflammasome of myeloid cells. These findings show that the commensal P. acnes-by activating the inflammasome-can trigger an innate immune response in the skin, thus establishing the NLRP3-inflammasome and IL-1β as possible therapeutic targets in acne.

Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

“…Likewise, TGFb decreases sebaceous gland lipid production 23 which is increased and altered in acne 24,25 . Finally, innate immune responses, elicited during microbial colonization by P. acnes 26,27 , may be modulated by TGFb 28 . Accordingly, transcript levels of TGFB2 were significantly reduced in fresh inflammatory acne papules in comparison with normal skin (Fig.…”

Inflammasomes

“…For instance, Francisella tularensis induces AIM2-mediated inflammatory responses in the skin during subcutaneous infection ) and NLRP3 is activated by the skin commensal Propionibacterium acnes (Kistowska et al 2014), by hepatitis C virus in hepatic macrophages (Burdette et al 2012), and by encephalomyocarditis virus through the viroporin 2B (Ito et al 2012). Systemically, CD4 T cells are subject to HIV-induced IFI16 activation, which leads to caspase-1-mediated pyroptosis and subsequent CD4 T-cell depletion Monroe et al 2014).…”

Immunocytokinetic aspects of the pathogenesis of acne

“…Показано, что воспалительный процесс у пациентов с акне поддерживается полинуклеарными нейтро-филами, продуцирующими большое количество свободных радикалов, простагландинами, лейко-триеном В4 и комплементом [1,14].…”

“…Вы-явлено также, что при УБ антигены клеточной стен-ки P. acnes активируют систему комплемента и обе-спечивают миграцию свободных радикалов, ней-трофилов, макрофагов в зону СВФ, в которой начи-нается продукция протеолитических ферментов, IL-1α, IL-1β и IL-8, TNF-γ, вызывающих дальней-шее развитие воспаления и выход содержимого же-лезы в дерму, провоцируя «запуск» каскада механиз-мов заболевания [6,14,17,18].…”