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: Magdalena Kistowska, Samuel Gehrke, Dragana Jankovic, Katrin Kerl, Antonia Fettelschoss, Laurence Feldmeyer, Gabriele Fenini, Antonios Kolios, Alexander Navarini, Ruta Ganceviciene, Jürgen Schauber, Emmanuel Contassot, Lars E French
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 134 Issue 3 Pg. 677-685 (Mar 2014) ISSN: 1523-1747 [Electronic] United States
• PMID: 24157462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• IL1B protein, human
• IL1B protein, mouse
• Inflammasomes
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• RNA, Small Interfering

Topics

• Acne Vulgaris (immunology, metabolism, microbiology)
• Animals
• Carrier Proteins (immunology, metabolism)
• Cell Line, Tumor
• Disease Models, Animal
• Gram-Positive Bacterial Infections (immunology, metabolism)
• Humans
• Inflammasomes (immunology, metabolism)
• Interleukin-1beta (genetics, immunology, metabolism)
• Keratinocytes (cytology, immunology, microbiology)
• Leukemia
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Monocytes (cytology, immunology, microbiology)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Phagocytosis (immunology)
• Propionibacterium acnes (immunology)
• RNA, Small Interfering (genetics)