Gimblet Ciara, Meisel Jacquelyn S, Loesche Michael A, Cole Stephen D, Horwinski Joseph, Novais Fernanda O, Misic Ana M, Bradley Charles W, Beiting Daniel P, Rankin Shelley C, Carvalho Lucas P, Carvalho Edgar M, Scott Phillip, Grice Elizabeth A
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Host Microbe. 2017 Jul 12;22(1):13-24.e4. doi: 10.1016/j.chom.2017.06.006. Epub 2017 Jun 29.
Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice. This observation allowed us to test whether a pre-existing dysbiotic skin microbiota influences disease, and we found that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results in exacerbated skin inflammatory responses. These findings demonstrate that a dysbiotic skin microbiota is not only a consequence of tissue stress, but also enhances inflammation, which has implications for many inflammatory cutaneous diseases.
皮肤微生物群可影响过敏和自身免疫反应、伤口愈合以及抗菌防御。我们研究了皮肤微生物群在皮肤利什曼病中的作用，发现感染巴西利什曼原虫的人类患者会出现皮肤微生物群失调，其特征是葡萄球菌和/或链球菌的丰度增加。感染硕大利什曼原虫的小鼠根据疾病严重程度表现出类似变化。重要的是，这种失调不仅限于病变部位，还可传播至远离感染部位的正常皮肤以及同笼饲养的未感染小鼠的皮肤。这一观察结果使我们能够测试预先存在的失调皮肤微生物群是否会影响疾病，我们发现用硕大利什曼原虫攻击失调的未感染小鼠或测试接触性超敏反应会导致皮肤炎症反应加剧。这些发现表明，失调的皮肤微生物群不仅是组织应激的结果，还会加剧炎症，这对许多炎症性皮肤病具有重要意义。
