Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
Department of Medicine, Division of Infectious Disease, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Infect Immun. 2021 Apr 16;89(5). doi: 10.1128/IAI.00647-20.
Group B (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.
B 群链球菌（GBS）是一种机会致病菌，可导致定植孕妇早产，并引发严重的新生儿疾病。尽管人们对导致 GBS 相关发病机制的许多问题仍不清楚，但目前尚不清楚为何 GBS 菌株的毒力差异如此之大。先前，我们证明了不同序列型（ST）和荚膜（CPS）型的 GBS 菌株在感染的 THP-1 巨噬样细胞中诱导不同的细胞因子谱。在这里，我们利用同一组遗传多样性的 GBS 分离株，通过评估 ST 和 CPS 特异性的细胞死亡和炎症信号通路差异，对这些研究进行了扩展。我们的结果表明，特别毒力的 ST 和 CPS 型，如 ST-17 和 CPS III 组，在 GBS 感染巨噬细胞后，与其他 ST 或 CPS 组相比，可诱导更强的 Jun-N-末端蛋白激酶（JNK）和 NF-κB 信号通路激活。此外，我们发现 ST-17、CPS III 和 CPS V GBS 菌株在感染过程中诱导最高水平的巨噬细胞死亡，并具有更强的内化和吞噬后在巨噬细胞中存活的能力。这些数据进一步支持了这样一种假设，即宿主对 GBS 的固有免疫反应存在差异，这对发病机制有重大影响，部分原因是 GBS 分离株之间存在基因型和表型差异。这些和类似的研究可能为针对侵袭性 GBS 感染的改进诊断、预防或治疗策略的制定提供信息。
