Division of Pediatric Infectious Diseases and Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Division of Infectious Diseases, Department of Pediatrics, UCSD, San Diego, California, USA.
JCI Insight. 2019 Mar 7;4(5). doi: 10.1172/jci.insight.124687.
Genomic studies revealed the existence of health- and acne-associated P. acnes strains and suggested novel approaches for broadening understanding of acne vulgaris. However, clinical association of P. acnes with disease or health has yet to be corroborated experimentally. Current animal models of acne do not closely mimic human disease and have unclear translational value. We have developed a murine model of acne by combining P. acnes inoculation with topical application of a synthetic human sebum. We showed that human sebum promoted persistence of intradermally injected P. acnes with little loss of viability after 1 week and permitted use of more physiologic inoculums. Application of acne-associated P. acnes RT4/5 strains led to development of moderate to severe skin pathology compared with application of health-associated type II P. acnes strains (RT2/6). RT4/5 P. acnes strains uniformly induced higher levels of KC (IL-8), IL-1α, IL-1β, and IL-6 in vitro and in vivo compared with type II P. acnes strains. Overall, our data provide immunopathologic corroboration of health and disease association of clinical P. acnes strains and inform on a platform to query putative virulence factors uncovered by genomic studies.
基因组研究揭示了与健康和痤疮相关的 P. acnes 菌株的存在，并提出了新的方法来拓宽对寻常痤疮的理解。然而，P. acnes 与疾病或健康的临床关联尚未通过实验得到证实。目前的痤疮动物模型不能很好地模拟人类疾病，并且其转化价值尚不清楚。我们通过将 P. acnes 接种与合成人皮脂的局部应用相结合，开发了一种痤疮的小鼠模型。我们表明，人皮脂促进了皮内注射的 P. acnes 的持续存在，在 1 周后几乎没有失去活力，并且允许使用更生理的接种物。与应用健康相关的 II 型 P. acnes 菌株 (RT2/6) 相比，应用与痤疮相关的 RT4/5 菌株会导致中度至重度皮肤病理学的发展。与 II 型 P. acnes 菌株相比，RT4/5 P. acnes 菌株在体外和体内均均匀诱导更高水平的 KC (IL-8)、IL-1α、IL-1β 和 IL-6。总的来说，我们的数据为临床 P. acnes 菌株的健康和疾病关联提供了免疫病理学证实，并为查询基因组研究中发现的假定毒力因子提供了一个平台。
