Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage

Karl-Jan Spittaels; Katleen van Uytfanghe; Christos C Zouboulis; Christophe Stove; Aurélie Crabbé; Tom Coenye

doi:10.1016/j.isci.2021.102575

Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K⁺ leakage

iScience. 2021 May 21;24(6):102575. doi: 10.1016/j.isci.2021.102575. eCollection 2021 Jun 25.

Authors

Karl-Jan Spittaels¹, Katleen van Uytfanghe², Christos C Zouboulis³, Christophe Stove², Aurélie Crabbé¹, Tom Coenye¹

Affiliations

¹ Laboratory of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium.
² Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium.
³ Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, 06847 Dessau, Germany.

Abstract

Some Cutibacterium acnes subgroups dominate on healthy skin, whereas others are frequently acne associated. Here we provide mechanistic insights into this difference, using an anaerobic keratinocyte-sebocyte-C. acnes co-culture model. An acneic C. acnes strain as well as its porphyrins activates NRLP3 inflammasome assembly, whereas this was not observed with a non-acneic strain. Low levels of intracellular K⁺ in keratinocytes stimulated with extracted porphyrins or infected with the acneic strain were observed, identifying porphyrin-induced K⁺ leakage as trigger for inflammasome activation. Using a panel of C. acnes strains, we found that porphyrin production and IL-1β release are correlated and are higher in acneic strains. This demonstrates that the latter produce more porphyrins, which interact with the keratinocyte cell membrane, leading to K⁺ leakage, NLRP3 inflammasome activation, and IL-1β release and provides an explanation for the observation that some C. acnes strains are associated with healthy skin, whereas others dominate in acneic skin.

Keywords: Immunology; Microbiology.