摘要:SummarySomeCutibacterium acnessubgroups dominate on healthy skin, whereas others are frequently acne associated. Here we provide mechanistic insights into this difference, using an anaerobic keratinocyte-sebocyte-C. acnesco-culture model. An acneicC. acnesstrain 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 ofC. acnesstrains, 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 someC. acnesstrains are associated with healthy skin, whereas others dominate in acneic skin.Graphical abstractDisplay OmittedHighlights•We developed an anaerobic keratinocyte-sebocyte-C. acnesco-culture model•AcneicC. acnesstrains and their porphyrins activate NRLP3 inflammasome assembly•Activation of the NRLP3 inflammasome is not observed in non-acneic strains•Porphyrins from acneicC. acnesactivate the inflammasome by inducing K+leakageImmunology; Microbiology