Recent advances in understanding inflammatory acne: Deciphering the relationship between Cutibacterium acnes and Th17 inflammatory pathway.
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
received:
13
04
2022
accepted:
18
10
2022
entrez:
2
2
2023
pubmed:
3
2
2023
medline:
7
2
2023
Statut:
ppublish
Résumé
Acne vulgaris is a common chronic inflammatory skin disease of the pilosebaceous units. Four factors contribute to acne: hyperseborrhea and dysseborrhea, follicular hyperkeratinisation, skin microbiome dysbiosis and local immuno-inflammation. Recent key studies have highlighted a better understanding of the important role of Cutibacterium acnes (C. acnes) in the development of acne. Three major findings in the last decade include: (1) the ability of C. acnes to self-organize in a biofilm associated with a more virulent activity, (2) the loss of the C. acnes phylotype diversity and (3) the central role of the Th17 pathway in acne inflammation. Indeed, there is a close link between C. acnes and the activation of the Th17 immuno-inflammatory pathway at the initiation of acne development. These mechanisms are directly linked to the loss of C. acnes phylotype diversity during acne, with a predominance of the pro-pathogenic phylotype IA1. This specifically contributes to the induction of the Th17-mediated immuno-inflammatory response involving skin cells, such as keratinocytes, monocytes and sebocytes. These advancements have led to new insights into the underlying mechanisms which can be harnessed to develop novel treatments and diagnostic biomarkers. A major disadvantage of traditional treatment with topical antibiotics is that they induce cutaneous dysbiosis and antimicrobial resistance. Thus, future treatments would no longer aim to 'kill' C. acnes, but to maintain the skin microbiota balance allowing for tissue homeostasis, specifically, the restoration of C. acnes phylotype diversity. Here, we provide an overview of some of the key processes involved in the pathogenesis of acne, with a focus on the prominent role of C. acnes and the Th17-inflammatory pathways involved.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3-11Informations de copyright
© 2023 European Academy of Dermatology and Venereology.
Références
Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2163-96.
Stathakis V, Kilkenny M, Marks R. Descriptive epidemiology of acne vulgaris in the community. Australas J Dermatol. 1997;38:115-23.
Gebauer K. Acne in adolescents. Aust Fam Physician. 2017;46:892-5.
Heng AHS, Chew FT. Systematic review of the epidemiology of acne vulgaris. Sci Rep. 2020;10:5754-4.
Rocha MA, Bagatin E. Adult-onset acne: prevalence, impact, and management challenges. Clin Cosmet Investig Dermatol. 2018;11:59-69.
Collier CN, Harper JC, Cafardi JA, Cantrell WC, Wang W, Foster KW, et al. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 2008;58:56-9.
Perkins AC, Maglione J, Hillebrand GG, Miyamoto K, Kimball AB. Acne vulgaris in women: prevalence across the life span. J Womens Health (Larchmt). 2012;21:223-30.
Poli F, Dreno B, Verschoore M. An epidemiological study of acne in female adults: results of a survey conducted in France. J Eur Acad Dermatol Venereol. 2001;15:541-5.
Dreno B, Poli F. Epidemiology of acne. Dermatology. 2003;206:7-10.
Walton S, Wyatt EH, Cunliffe WJ. Genetic control of sebum excretion and acne - a twin study. Br J Dermatol. 1988;118:393-6.
Petridis C, Navarini AA, Dand N, Saklatvala J, Baudry D, Duckworth M, et al. Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne. Nat Commun. 2018;9:5075.
Krutmann J, Moyal D, Liu W, Kandahari S, Lee GS, Nopadon N, et al. Pollution and acne: is there a link? Clin Cosmet Investig Dermatol. 2017;10:199-204.
Burns EM, Ahmed H, Isedeh PN, Kohli I, Van Der Pol W, Shaheen A, et al. Ultraviolet radiation, both UVA and UVB, influences the composition of the skin microbiome. Exp Dermatol. 2019;28:136-41.
Tan JK, Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol. 2015;172(Suppl 1):3-12.
Juhl CR, Bergholdt HKM, Miller IM, Jemec GBE, Kanters JK, Ellervik C. Dairy intake and acne vulgaris: a systematic review and meta-analysis of 78,529 children, adolescents, and young adults. Nutrients. 2018;10:1049.
Adebamowo CA, Spiegelman D, Berkey CS, Danby FW, Rockett HH, Colditz GA, et al. Milk consumption and acne in teenaged boys. J Am Acad Dermatol. 2008;58:787-93.
Ghodsi SZ, Orawa H, Zouboulis CC. Prevalence, severity, and severity risk factors of acne in high school pupils: a community-based study. J Invest Dermatol. 2009;129:2136-41.
Wu TQ, Mei SQ, Zhang JX, Gong LF, Wu FJ, Wu WH, et al. Prevalence and risk factors of facial acne vulgaris among Chinese adolescents. Int J Adolesc Med Health. 2007;19:407-12.
Do TT, Zarkhin S, Orringer JS, Nemeth S, Hamilton T, Sachs D, et al. Computer-assisted alignment and tracking of acne lesions indicate that most inflammatory lesions arise from comedones and de novo. J Am Acad Dermatol. 2008;58:603-8.
Harder J, Tsuruta D, Murakami M, Kurokawa I. What is the role of antimicrobial peptides (AMP) in acne vulgaris? Exp Dermatol. 2013;22:386-91.
Bernales SA. Acne vulgaris: role of the immune system. Int J Dermatol. 2021;60:1076-81.
Zouboulis CC. Acne and sebaceous gland function. Clin Dermatol. 2004;22:360-6.
Saint-Leger D, Bague A, Lefebvre E, Cohen E, Chivot M. A possible role for squalene in the pathogenesis of acne. II. In vivo study of squalene oxides in skin surface and intra-comedonal lipids of acne patients. Br J Dermatol. 1986;114:543-52.
Clayton RW, Göbel K, Niessen CM, Paus R, van Steensel MAM, Lim X. Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis. Br J Dermatol. 2019;181:677-90.
Dreno B, Gollnick HP, Kang S, Thiboutot D, Bettoli V, Torres V, et al. Understanding innate immunity and inflammation in acne: implications for management. J Eur Acad Dermatol Venereol. 2015;29(Suppl 4):3-11.
Jeremy AH, Holland DB, Roberts SG, Thomson KF, Cunliffe WJ. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol. 2003;121:20-7.
Lee YB, Byun EJ, Kim HS. Potential role of the microbiome in acne: a comprehensive review. J Clin Med. 2019;8:987.
Abdallah F, Mijouin L, Pichon C. Skin immune landscape: inside and outside the organism. Mediators Inflamm. 2017;2017:5095293.
Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018;16:143-55.
Ramasamy S, Barnard E, Dawson TL Jr, Li H. The role of the skin microbiota in acne pathophysiology. Br J Dermatol. 2019;181:691-9.
Qidwai A, Pandey M, Pathak S, Kumar R, Dikshit A. The emerging principles for acne biogenesis: a dermatological problem of puberty. Hum Microbiome J. 2017;4:7-13.
Grice EA. The intersection of microbiome and host at the skin interface: genomic- and metagenomic-based insights. Genome Res. 2015;25:1514-20.
Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011;9:244-53.
Cunliffe WJ, Holland DB, Jeremy A. Comedone formation: etiology, clinical presentation, and treatment. Clin Dermatol. 2004;22:367-74.
Plewig G, Fulton JE, Kligman AM. Cellular dynamics of comedo formation in acne vulgaris. Arch Dermatol Forsch. 1971;242:12-29.
Josse G, Mias C, Le Digabel J, Filiol J, Ipinazar C, Villaret A, et al. High bacterial colonization and lipase activity in microcomedones. Exp Dermatol. 2020;29:168-76.
Tanghetti EA. The role of inflammation in the pathology of acne. J Clin Aesthet Dermatol. 2013;6:27-35.
Xu X, Ran X, Tang J, Pradhan S, Dai Y, Zhuang K, et al. Skin microbiota in non-inflammatory and inflammatory lesions of acne vulgaris: the underlying changes within the pilosebaceous unit. Mycopathologia. 2021;186(Suppl 5):863-869.
Dréno B, Dagnelie MA, Khammari A, Corvec S. The skin microbiome: a new actor in inflammatory acne. Am J Clin Dermatol. 2020;21:18-24.
Dagnelie MA, Corvec S, Saint-Jean M, Nguyen JM, Khammari A, Dréno B. Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process. J Eur Acad Dermatol Venereol. 2019;33:2340-8.
McDowell A, Perry AL, Lambert PA, Patrick S. A new phylogenetic group of Propionibacterium acnes. J Med Microbiol. 2008;57:218-24.
Fitz-Gibbon S, Tomida S, Chiu BH, Nguyen L, Du C, Liu M, et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Invest Dermatol. 2013;133:2152-60.
Omer H, McDowell A, Alexeyev OA. Understanding the role of Propionibacterium acnes in acne vulgaris: the critical importance of skin sampling methodologies. Clin Dermatol. 2017;35:118-29.
Miura Y, Ishige I, Soejima N, Suzuki Y, Uchida K, Kawana S, et al. Quantitative PCR of Propionibacterium acnes DNA in samples aspirated from sebaceous follicles on the normal skin of subjects with or without acne. J Med Dent Sci. 2010;57:65-74.
Jahns AC, Eilers H, Ganceviciene R, Alexeyev OA. Propionibacterium species and follicular keratinocyte activation in acneic and normal skin. Br J Dermatol. 2015;172:981-7.
Leyden JJ, McGinley KJ, Vowels B. Propionibacterium acnes colonization in acne and nonacne. Dermatology. 1998;196:55-8.
Zhang N, Yuan R, Xin KZ, Lu Z, Ma Y. Antimicrobial susceptibility, biotypes and phylotypes of clinical cutibacterium (formerly propionibacterium) acnes strains isolated from acne patients: an observational study. Dermatol Ther (Heidelb). 2019;9:735-46.
Barnard E, Shi B, Kang D, Craft N, Li H. The balance of metagenomic elements shapes the skin microbiome in acne and health. Sci Rep. 2016;6:39491.
Dagnelie MA, Montassier E, Khammari A, Mounier C, Corvec S, Dréno B. Inflammatory skin is associated with changes in the skin microbiota composition on the back of severe acne patients. Exp Dermatol. 2019;28:961-7.
McDowell A, Nagy I, Magyari M, Barnard E, Patrick S. The opportunistic pathogen Propionibacterium acnes: insights into typing, human disease, clonal diversification and CAMP factor evolution. PLoS One. 2013;8:e70897.
Melnik BC. Linking diet to acne metabolomics, inflammation, and comedogenesis: an update. Clin Cosmet Investig Dermatol. 2015;8:371-88.
Yu Y, Champer J, Agak GW, Kao S, Modlin RL, Kim J. Different Propionibacterium acnes phylotypes induce distinct immune responses and express unique surface and secreted proteomes. J Invest Dermatol. 2016;136:2221-8.
McDowell A, Barnard E, Nagy I, Gao A, Tomida S, Li H, et al. An expanded multilocus sequence typing scheme for Propionibacterium acnes: investigation of ‘pathogenic’, ‘commensal’ and antibiotic resistant strains. PLoS One. 2012;7:e41480.
Lomholt HB, Scholz CFP, Brüggemann H, Tettelin H, Kilian M. A comparative study of Cutibacterium (Propionibacterium) acnes clones from acne patients and healthy controls. Anaerobe. 2017;47:57-63.
Brzuszkiewicz E, Weiner J, Wollherr A, Thürmer A, Hüpeden J, Lomholt HB, et al. Comparative genomics and transcriptomics of Propionibacterium acnes. PLoS One. 2011;6:e21581.
Jahns AC, Eilers H, Alexeyev OA. Transcriptomic analysis of Propionibacterium acnes biofilms in vitro. Anaerobe. 2016;42:111-8.
Beylot C, Auffret N, Poli F, Claudel JP, Leccia MT, Del Giudice P, et al. Propionibacterium acnes: an update on its role in the pathogenesis of acne. J Eur Acad Dermatol Venereol. 2014;28:271-8.
Jahns AC, Lundskog B, Ganceviciene R, Palmer RH, Golovleva I, Zouboulis CC, et al. An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study. Br J Dermatol. 2012;167:50-8.
Gannesen AV, Zdorovenko EL, Botchkova EA, Hardouin J, Massier S, Kopitsyn DS, et al. Composition of the biofilm matrix of Cutibacterium acnes acneic strain RT5. Front Microbiol. 2019;10:1284.
Burkhart CN, Burkhart CG. Microbiology's principle of biofilms as a major factor in the pathogenesis of acne vulgaris. Int J Dermatol. 2003;42:925-7.
Burkhart CG, Burkhart CN. Expanding the microcomedone theory and acne therapeutics: Propionibacterium acnes biofilm produces biological glue that holds corneocytes together to form plug. J Am Acad Dermatol. 2007;57:722-4.
Coenye T, Peeters E, Nelis HJ. Biofilm formation by Propionibacterium acnes is associated with increased resistance to antimicrobial agents and increased production of putative virulence factors. Res Microbiol. 2007;158:386-92.
Kuehnast T, Cakar F, Weinhäupl T, Pilz A, Selak S, Schmidt MA, et al. Comparative analyses of biofilm formation among different Cutibacterium acnes isolates. Int J Med Microbiol. 2018;308:1027-35.
Brüggemann H. Insights in the pathogenic potential of Propionibacterium acnes from its complete genome. Semin Cutan Med Surg. 2005;24:67-72.
Brüggemann H, Henne A, Hoster F, Liesegang H, Wiezer A, Strittmatter A, et al. The complete genome sequence of Propionibacterium acnes, a commensal of human skin. Science. 2004;305:671-3.
Mayslich C, Grange PA, Dupin N. Cutibacterium acnes as an opportunistic pathogen: an update of its virulence-associated factors. Microorganisms. 2021;9:303.
Tomida S, Nguyen L, Chiu BH, Liu J, Sodergren E, Weinstock GM, et al. Pan-genome and comparative genome analyses of Propionibacterium acnes reveal its genomic diversity in the healthy and diseased human skin microbiome. MBio. 2013;4:e00003-00013.
Christensen GJ, Brüggemann H. Bacterial skin commensals and their role as host guardians. Benef Microbes. 2014;5:201-15.
Holland C, Mak TN, Zimny-Arndt U, Schmid M, Meyer TF, Jungblut PR, et al. Proteomic identification of secreted proteins of Propionibacterium acnes. BMC Microbiol. 2010;10:230.
Farrar MD, Ingham E, Holland KT. Heat shock proteins and inflammatory acne vulgaris: molecular cloning, overexpression and purification of a Propionibacterium acnes GroEL and DnaK homologue. FEMS Microbiol Lett. 2000;191:183-6.
Bek-Thomsen M, Lomholt HB, Scavenius C, Enghild JJ, Brüggemann H. Proteome analysis of human sebaceous follicle infundibula extracted from healthy and acne-affected skin. PLoS One. 2014;9:e107908.
Contassot E, French LE. New insights into acne pathogenesis: Propionibacterium acnes activates the inflammasome. J Invest Dermatol. 2014;134:310-3.
Decker LC, Deuel DM, Sedlock DM. Role of lipids in augmenting the antibacterial activity of benzoyl peroxide against Propionibacterium acnes. Antimicrob Agents Chemother. 1989;33:326-30.
Valanne S, McDowell A, Ramage G, Tunney MM, Einarsson GG, O'Hagan S, et al. CAMP factor homologues in Propionibacterium acnes: a new protein family differentially expressed by types I and II. Microbiology (Reading). 2005;151:1369-79.
Johnson T, Kang D, Barnard E, Li H. Strain-level differences in porphyrin production and regulation in Propionibacterium acnes elucidate disease associations. mSphere. 2016;1:e00023-15.
Borrel V, Gannesen AV, Barreau M, Gaviard C, Duclairoir-Poc C, Hardouin J, et al. Adaptation of acneic and non acneic strains of Cutibacterium acnes to sebum-like environment. Microbiology. 2019;8:e00841.
Lwin SM, Kimber I, McFadden JP. Acne, quorum sensing and danger. Clin Exp Dermatol. 2014;39:162-7.
Maddur MS, Miossec P, Kaveri SV, Bayry J. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol. 2012;181:8-18.
Bernardini N, Skroza N, Tolino E, Mambrin A, Anzalone A, Balduzzi V, et al. IL-17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art. Int J Dermatol. 2020;59:406-11.
Kelhälä HL, Palatsi R, Fyhrquist N, Lehtimäki S, Väyrynen JP, Kallioinen M, et al. IL-17/Th17 pathway is activated in acne lesions. PLoS One. 2014;9:e105238.
Agak GW, Qin M, Nobe J, Kim MH, Krutzik SR, Tristan GR, et al. Propionibacterium acnes induces an IL-17 response in acne vulgaris that is regulated by vitamin a and vitamin D. J Invest Dermatol. 2014;134:366-73.
Farrar MD, Ingham E. Acne: inflammation. Clin Dermatol. 2004;22:380-4.
Norris JFB, Cunliffe WJ. A histological and immunocytochemical study of early acne lesions. Br J Dermatol. 1988;118:651-9.
Eliasse Y, Leveque E, Garidou L, Battut L, McKenzie B, Nocera T, et al. IL-17(+) mast cell/T helper cell Axis in the early stages of acne. Front Immunol. 2021;12:740540.
Ebrahim AA, Mustafa AI, El-Abd AM. Serum interleukin-17 as a novel biomarker in patients with acne vulgaris. J Cosmet Dermatol. 2019;18:1975-9.
Farag AGA, Maraee AH, Rifaat Al-Sharaky D, Elshaib ME, Kohla MSM, Shehata WA. Tissue expression of IL-17A and FOXP3 in acne vulgaris patients. J Cosmet Dermatol. 2021;20:330-7.
Kistowska M, Meier B, Proust T, Feldmeyer L, Cozzio A, Kuendig T, et al. Propionibacterium acnes promotes Th17 and Th17/Th1 responses in acne patients. J Invest Dermatol. 2015;135:110-8.
Gallo RL, Nakatsuji T. Microbial symbiosis with the innate immune defense system of the skin. J Invest Dermatol. 2011;131:1974-80.
Tohyama M, Hanakawa Y, Shirakata Y, Dai X, Yang L, Hirakawa S, et al. IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression. Eur J Immunol. 2009;39:2779-88.
Jugeau S, Tenaud I, Knol AC, Jarrousse V, Quereux G, Khammari A, et al. Induction of toll-like receptors by Propionibacterium acnes. Br J Dermatol. 2005;153:1105-13.
Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133-41.
Agak GW, Kao S, Ouyang K, Qin M, Moon D, Butt A, et al. Phenotype and antimicrobial activity of Th17 cells induced by Propionibacterium acnes strains associated with healthy and acne skin. J Invest Dermatol. 2018;138:316-24.
Kim J, Ochoa M-T, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, et al. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol. 2002;169:1535-41.
Mattii M, Lovászi M, Garzorz N, Atenhan A, Quaranta M, Lauffer F, et al. Sebocytes contribute to skin inflammation by promoting the differentiation of T helper 17 cells. Br J Dermatol. 2018;178:722-30.
Kupper TS, Fuhlbrigge RC. Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol. 2004;4:211-22.
Nagy I, Pivarcsi A, Kis K, Koreck A, Bodai L, McDowell A, et al. Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. Microbes Infect. 2006;8:2195-205.
Nakatsuji T, Liu YT, Huang CP, Zoubouis CC, Gallo RL, Huang CM. Antibodies elicited by inactivated Propionibacterium acnes-based vaccines exert protective immunity and attenuate the IL-8 production in human sebocytes: relevance to therapy for acne vulgaris. J Invest Dermatol. 2008;128:2451-7.
Sardana K, Verma G. Propionibacterium acnes and the Th1/Th17 Axis, implications in acne pathogenesis and treatment. Indian J Dermatol. 2017;62:392-4.
Huang YC, Yang CH, Li TT, Zouboulis CC, Hsu HC. Cell-free extracts of Propionibacterium acnes stimulate cytokine production through activation of p38 MAPK and toll-like receptor in SZ95 sebocytes. Life Sci. 2015;139:123-31.
Thiboutot DM, Layton AM, Anne EE. IL-17: a key player in the P. acnes inflammatory cascade? J Invest Dermatol. 2014;134:307-10.
Demina OM, Kartelishev A, Karpova E, Danischuk O. Role of cytokines in the pathogenesis of acne. Int J Biomed. 2017;7:37-40.
Cibrián D, Sánchez-Madrid F. CD69: from activation marker to metabolic gatekeeper. Eur J Immunol. 2017;47:946-53.
Gervason S, Metton I, Gemrot E, Ranouille E, Skorski G, Cabannes M, et al. Rhodomyrtus tomentosa fruit extract and skin microbiota: a focus on C. acnes phylotypes in acne subjects. Cosmetics. 2020;7:53.
Fournière M, Latire T, Souak D, Feuilloley MGJ, Bedoux G. Staphylococcus epidermidis and Cutibacterium acnes: two major sentinels of skin microbiota and the influence of cosmetics. Microorganisms. 2020;8:1752.
Dréno B, Pécastaings S, Corvec S, Veraldi S, Khammari A, Roques C. Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates. J Eur Acad Dermatol Venereol. 2018;32(Suppl 2):5-14.
Lam M, Hu A, Fleming P, Lynde CW. The impact of acne treatment on skin bacterial microbiota: a systematic review. J Cutan Med Surg. 2022;26:93-7.
Wang Y, Hata TR, Tong YL, Kao MS, Zouboulis CC, Gallo RL, et al. The anti-inflammatory activities of Propionibacterium acnes CAMP Factir-Targeted acne vaccines. J Invest Dermatol. 2018;18:2355-2364.
Yu Y, Dunaway S, Champer J, Kim J, Alikhan A. Changing our microbiome: probiotics in dermatology. Br J Dermatol. 2020;182:39-46.
Farfin J, Gonzalez J.M & Vives M. The immunomodulatory potential of phage therapy to treat acne: a review on bacterial lysis and immunomodulation. Peer J. 2022;10:e13553. https://doi.org/10.7717/peerj.13553
Goodman G. Cleansing and moisturizing in acne patients. Am J Clin Dermatol. 2009;10(Suppl 1):1-6.