title: 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.
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kistowska
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Gehrke
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Dragana
authors.initials: D
authors.lastname: Jankovic
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kerl
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Antonia
authors.initials: A
authors.lastname: Fettelschoss
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Feldmeyer
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fenini
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Antonios
authors.initials: A
authors.lastname: Kolios
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Navarini
authors.affiliation: Centre of Dermatovenereology, Vilnius University Hospital, Vilnius, Lithuania.
authors.forename: Ruta
authors.initials: R
authors.lastname: Ganceviciene
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schauber
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Contassot
authors.affiliation: Department of Dermatology, University Hospital, Zürich, Switzerland. Electronic address: lars.french@usz.ch.
authors.forename: Lars E
authors.initials: LE
authors.lastname: French
mesh_terms: D000152:Acne Vulgaris / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D007938:Leukemia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010587:Phagocytosis / Q000276:immunology; D011425:Propionibacterium acnes / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C508585:IL1B protein, human; C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D034741:RNA, Small Interfering