Distinct Group B Streptococcus Sequence and Capsule Types Differentially Impact Macrophage Stress and Inflammatory Signaling Responses.
Distinct Group B Streptococcus Sequence and Capsule Types Differentially Impact Macrophage Stress and Inflammatory Signaling Responses.
复制标题
不同的B族链球菌序列和荚膜类型不同地影响巨噬细胞应激和炎症信号应答。
DOI：
10.1128/iai.00647-20
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发表时间：
2021-04-16
影响因子：
3.1
通讯作者：
Manning SD
中科院分区：
文献类型：
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作者：
Flaherty RA;Aronoff DM;Gaddy JA;Petroff MG;Manning SD
B群链球菌（GBS）是一种机会性细菌病原体，可导致定植的孕妇早产和严重的新生儿疾病。关于驱动GBS相关发病机制的许多问题仍未得到解答，并且尚不清楚为什么在GBS菌株之间观察到的毒力差异如此之大。B群链球菌（GBS）是一种机会性细菌病原体，可导致定植的孕妇早产和严重的新生儿疾病。关于驱动GBS相关发病机制的许多问题仍未得到解答，并且尚不清楚为什么在GBS菌株之间观察到的毒力差异如此之大。之前，我们证明了不同序列型（STs）和胶囊型（CPS）的GBS菌株在感染的THP-1巨噬细胞样细胞中诱导不同的细胞因子谱。在这里，我们通过利用同一组遗传多样性的GBS分离物来扩展这些研究，以评估ST和cps在上游细胞死亡和炎症信号通路中的特异性差异。我们的研究结果表明，与其他ST或CPS组相比，毒性特别强的ST和CPS类型，如ST-17和CPS III组，在GBS感染巨噬细胞后诱导jun - n端蛋白激酶（JNK）和NF-κB通路激活增强。此外，我们发现ST-17、CPS III和CPS V GBS菌株在感染期间诱导巨噬细胞死亡的水平最高，并且在吞噬后表现出更明显的内化能力和在巨噬细胞中存活的能力。这些数据进一步支持了一种假设，即宿主对GBS的可变先天免疫反应在一定程度上源于GBS分离株之间的基因型和表型差异，而这种反应对GBS的发病机制有重要影响。这些和类似的研究可能为改进针对侵袭性GBS感染的诊断、预防或治疗策略的发展提供信息。
Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that can contribute to the induction of preterm birth in colonized pregnant women and to severe neonatal disease. Many questions regarding the mechanisms that drive GBS-associated pathogenesis remain unanswered, and it is not yet clear why virulence has been observed to vary so extensively across GBS strains. Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that can contribute to the induction of preterm birth in colonized pregnant women and to severe neonatal disease. Many questions regarding the mechanisms that drive GBS-associated pathogenesis remain unanswered, and it is not yet clear why virulence has been observed to vary so extensively across GBS strains. Previously, we demonstrated that GBS strains of different sequence types (STs) and capsule (CPS) types induce different cytokine profiles in infected THP-1 macrophage-like cells. Here, we expanded on these studies by utilizing the same set of genetically diverse GBS isolates to assess ST and CPS-specific differences in upstream cell death and inflammatory signaling pathways. Our results demonstrate that particularly virulent STs and CPS types, such as the ST-17 and CPS III groups, induce enhanced Jun-N-terminal protein kinase (JNK) and NF-κB pathway activation following GBS infection of macrophages compared with other ST or CPS groups. Additionally, we found that ST-17, CPS III, and CPS V GBS strains induce the greatest levels of macrophage cell death during infection and exhibit a more pronounced ability to be internalized and to survive in macrophages following phagocytosis. These data provide further support for the hypothesis that variable host innate immune responses to GBS, which significantly impact pathogenesis, stem in part from genotypic and phenotypic differences among GBS isolates. These and similar studies may inform the development of improved diagnostic, preventive, or therapeutic strategies targeting invasive GBS infections.