Ferreirinha Pedro, Pérez-Cabezas Begoña, Correia Alexandra, Miyazawa Bruna, França Angela, Carvalhais Virgínia, Faustino Augusto, Cordeiro-da-Silva Anabela, Teixeira Luzia, Pier Gerald B, Cerca Nuno, Vilanova Manuel
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ICBAS-UP, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal.
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Infect Immun. 2016 Sep 19;84(10):2933-43. doi: 10.1128/IAI.00290-16. Print 2016 Oct.
Poly-N-acetylglucosamine (PNAG) is a major component of the Staphylococcus epidermidis biofilm extracellular matrix. However, it is not yet clear how this polysaccharide impacts the host immune response and infection-associated pathology. Faster neutrophil recruitment and bacterial clearance were observed in mice challenged intraperitoneally with S. epidermidis biofilm cells of the PNAG-producing 9142 strain than in mice similarly challenged with the isogenic PNAG-defective M10 mutant. Moreover, intraperitoneal priming with 9142 cells exacerbated liver inflammatory pathology induced by a subsequent intravenous S. epidermidis challenge, compared to priming with M10 cells. The 9142-primed mice had elevated splenic CD4(+) T cells producing gamma interferon and interleukin-17A, indicating that PNAG promoted cell-mediated immunity. Curiously, despite having more marked liver tissue pathology, 9142-primed mice also had splenic T regulatory cells with greater suppressive activity than those of their M10-primed counterparts. By showing that PNAG production by S. epidermidis biofilm cells exacerbates host inflammatory pathology, these results together suggest that this polysaccharide contributes to the clinical features associated with biofilm-derived infections.
聚-N-乙酰葡糖胺（PNAG）是表皮葡萄球菌生物膜细胞外基质的主要成分。然而，这种多糖如何影响宿主免疫反应和感染相关病理仍不清楚。与用同基因PNAG缺陷型M10突变体进行类似腹腔攻击的小鼠相比，用产生PNAG的9142菌株的表皮葡萄球菌生物膜细胞进行腹腔攻击的小鼠中观察到更快的中性粒细胞募集和细菌清除。此外，与用M10细胞进行预刺激相比，用9142细胞进行腹腔预刺激会加剧随后静脉注射表皮葡萄球菌攻击所诱导的肝脏炎症病理。用9142预刺激的小鼠脾脏中产生γ干扰素和白细胞介素-17A的CD4(+) T细胞增加，表明PNAG促进细胞介导的免疫。奇怪的是，尽管肝脏组织病理更明显，但用9142预刺激的小鼠脾脏中的调节性T细胞也比用M10预刺激的小鼠具有更强的抑制活性。通过表明表皮葡萄球菌生物膜细胞产生的PNAG会加剧宿主炎症病理，这些结果共同表明这种多糖促成了与生物膜源性感染相关的临床特征。
