Smeekens Sanne P, Huttenhower Curtis, Riza Anca, van de Veerdonk Frank L, Zeeuwen Patrick L J M, Schalkwijk Joost, van der Meer Jos W M, Xavier Ramnik J, Netea Mihai G, Gevers Dirk
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
J Innate Immun. 2014;6(3):253-62. doi: 10.1159/000351912. Epub 2013 Jun 22.
Chronic mucocutaneous candidiasis (CMC) and hyper-IgE syndrome (HIES) are primary immunodeficiencies mainly caused by mutations in STAT1 and STAT3, respectively. CMC and HIES patients have an increased risk for skin and mucosal infections with fungal pathogens and Staphylococcus aureus. However, it is unknown whether the genetic defects in these patients also affect the skin and mucosal microbiome, which in turn may influence host defense mechanisms.
The skin and oral microbiome of CMC and HIES patients was compared to that of healthy controls at five body sites using 16S rRNA sequencing. The influence of skin colonizers on the immune response was investigated using in vitro experiments.
The microbiome of CMC and HIES patients contained more Gram-negative bacteria, especially Acinetobacter spp., and less of the normal Corynebacterium spp. compared to healthy controls. Exposure of human primary leukocytes to Acinetobacter suppressed the cytokine response to Candida albicans and S. aureus, while the normal corynebacteria did not suppress cytokine responses.
These results demonstrate that central mediators of immune responses like STAT1 and STAT3 not only directly influence immune responses, but also result in changes in the skin microbiome that in turn can amplify the defective immune response against fungal and microbial pathogens.
慢性黏膜皮肤念珠菌病（CMC）和高免疫球蛋白E综合征（HIES）是主要分别由信号转导和转录激活因子1（STAT1）及信号转导和转录激活因子3（STAT3）突变引起的原发性免疫缺陷病。CMC和HIES患者皮肤和黏膜感染真菌病原体及金黄色葡萄球菌的风险增加。然而，这些患者的基因缺陷是否也会影响皮肤和黏膜微生物群，进而影响宿主防御机制尚不清楚。
采用16S核糖体RNA测序，比较了CMC和HIES患者与健康对照者五个身体部位的皮肤和口腔微生物群。利用体外实验研究了皮肤定植菌对免疫反应的影响。
与健康对照相比，CMC和HIES患者的微生物群含有更多革兰氏阴性菌，尤其是不动杆菌属，而正常棒状杆菌属较少。人原代白细胞暴露于不动杆菌会抑制对白色念珠菌和金黄色葡萄球菌的细胞因子反应，而正常棒状杆菌则不会抑制细胞因子反应。
这些结果表明，像STAT1和STAT3这样的免疫反应中枢介质不仅直接影响免疫反应，还会导致皮肤微生物群的变化，进而放大针对真菌和微生物病原体的免疫反应缺陷。
