Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage
Summary: 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 acti...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221005435 |
| _version_ | 1818440778098147328 |
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| author | Karl-Jan Spittaels Katleen van Uytfanghe Christos C. Zouboulis Christophe Stove Aurélie Crabbé Tom Coenye |
| author_facet | Karl-Jan Spittaels Katleen van Uytfanghe Christos C. Zouboulis Christophe Stove Aurélie Crabbé Tom Coenye |
| author_sort | Karl-Jan Spittaels |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-14T18:17:45Z |
| format | Article |
| id | doaj.art-b43d2ce4bb714a2ab7fffea39904a05c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T18:17:45Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b43d2ce4bb714a2ab7fffea39904a05c2022-12-21T22:52:09ZengElsevieriScience2589-00422021-06-01246102575Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakageKarl-Jan Spittaels0Katleen van Uytfanghe1Christos C. Zouboulis2Christophe Stove3Aurélie Crabbé4Tom Coenye5Laboratory of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, BelgiumLaboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, BelgiumDepartments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, 06847 Dessau, GermanyLaboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, BelgiumLaboratory of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, BelgiumLaboratory of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221005435ImmunologyMicrobiology |
| spellingShingle | Karl-Jan Spittaels Katleen van Uytfanghe Christos C. Zouboulis Christophe Stove Aurélie Crabbé Tom Coenye Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage iScience Immunology Microbiology |
| title | Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage |
| title_full | Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage |
| title_fullStr | Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage |
| title_full_unstemmed | Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage |
| title_short | Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K+ leakage |
| title_sort | porphyrins produced by acneic cutibacterium acnes strains activate the inflammasome by inducing k leakage |
| topic | Immunology Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221005435 |
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