Propionibacterium acnes–induced immunopathology correlates with health and disease association

Kolar, Stacey L.; Tsai, Chuen-Tinn; Torres, Juan; Fan, Xuemo; Li, Huiying; Liu, George Y.

doi:10.1172/jci.insight.124687

Cited by 37 publications

(40 citation statements)

References 40 publications

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“…However, there are few acne animal models that accurately recapitulate the situation in humans (e.g., in many models infection is not needed for the development of acne). A recently developed model in which acne lesions are induced by the combined application of C. acnes and human sebum could be a valuable alternative, although this model has several drawbacks as well, including the requirement for intradermal administration of C. acnes and the relatively acute nature of the infection ( Kolar et al., 2019 ). The use of skin biopsies is a possible alternative ( Jahns and Alexeyev, 2014 , 2016 ; Dagnelie et al., 2019 ; Jasson et al., 2013 ), but such biopsies are not easy to obtain and are small (i.e., would not necessarily always allow simultaneous analysis of microbial load and measurement of porphyrin and cytokine levels).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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“…C. acnes strains HL043PA1 (HM‐513), HL053PA1 (HM‐522) and HL110PA3 (HM‐554) were acquired from the Biodefense and Emerging Infections Research Resources Repository (BEI Resources, Manassas, VA), which were previously isolated at UCLA (Fitz‐Gibbon et al, 2013; Tomida et al, 2013). HM‐513 and HM‐522 are antibiotic‐resistant acne‐associated ribotype IA isolates, and HM‐554 is a ribotype II isolate from healthy human skin (Table 1) (Johnson, Kang, Barnard, & Li, 2016; Kolar et al, 2019). All C. acnes isolates were grown under anaerobic conditions (BD Diagnostic Systems) in BHI liquid and solid media (Sigma‐Aldrich, St. Louis, MO) at 37°C for 5 days to reach the stationary phase.…”

Section: Methodsmentioning

confidence: 99%

Caenorhabditis elegansmounts a p38MAPKpathway‐mediated defence toCutibacterium acnesinfection

Huang

Pan

Kim

et al. 2020

Cellular Microbiology

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Cutibacterium acnes is capable of inducing inflammation in acne and can lead to a chronic prostatic infection. The diverse pathogenicity among different strains of C. acnes has been presented, but simple appropriate animal models for the evaluation of this bacterium are lacking. In this study, the nematode Caenorhabditis elegans was used as an invertebrate infection model. We revealed that C. acnes type strain ATCC 6919 caused lethal infections to C. elegans in solid and liquid culture media (p < .0001). Compared with the strain ATCC 6919, the antibiotic‐resistant strain HM‐513 was more virulent, resulting in reduced survival (p < .0001). Four different C. acnes strains killed worms with a p value of less than .0001 when provided to C. elegans at 4.8 × 108 CFU/ml. The infection model was also employed to explore host defence responses. An increase in numerous immune effectors in response to C. acnes was detected. We focused on nine C‐type lectins, including: clec‐13, clec‐17, clec‐47, clec‐52, clec‐60, clec‐61, clec‐70, clec‐71 and clec‐227. The induced expression of these C‐type lectin genes was down‐regulated in mutant worms deficient in the p38 mitogen‐activated protein kinase (MAPK) pathway. Meanwhile, PMK‐1 (MAPK) was phosphorylated and activated at the onset of C. acnes infection. By monitoring the survival of mutant worms, we found that PMK‐1, SEK‐1 (MAPKK) and TIR‐1 (MAPKKK) were critical in responding to C. acnes infection. C. elegans pmk‐1 and tir‐1 mutants exhibited higher mortality to C. acnes infection (p < .0001). In conclusion, C. elegans serves as a simple and valuable model to study C. acnes virulence and facilitates improvements in understanding of host innate immune responses.

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“…5, C to F ). Here, skin pathology associated with acne was scored as following a previous literature ( 47 ) (the timing of medication administration, at which pathological score is above 4, is 3 to 5 days later in conventional treatment; see Materials and Methods and fig. S16 for details).…”

Section: Resultsmentioning

confidence: 99%

Diving beetle–like miniaturized plungers with reversible, rapid biofluid capturing for machine learning–based care of skin disease

et al. 2021

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Recent advances in bioinspired nano/microstructures have received attention as promising approaches with which to implement smart skin-interfacial devices for personalized health care. In situ skin diagnosis requires adaptable skin adherence and rapid capture of clinical biofluids. Here, we report a simple, all-in-one device consisting of microplungers and hydrogels that can rapidly capture biofluids and conformally attach to skin for stable, real-time monitoring of health. Inspired by the male diving beetle, the microplungers achieve repeatable, enhanced, and multidirectional adhesion to human skin in dry/wet environments, revealing the role of the cavities in these architectures. The hydrogels within the microplungers instantaneously absorb liquids from the epidermis for enhanced adhesiveness and reversibly change color for visual indication of skin pH levels. To realize advanced biomedical technologies for the diagnosis and treatment of skin, our suction-mediated device is integrated with a machine learning framework for accurate and automated colorimetric analysis of pH levels.

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Propionibacterium acnes–induced immunopathology correlates with health and disease association

Cited by 37 publications

References 40 publications

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

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

Caenorhabditis elegansmounts a p38MAPKpathway‐mediated defence toCutibacterium acnesinfection

Diving beetle–like miniaturized plungers with reversible, rapid biofluid capturing for machine learning–based care of skin disease

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