Korir Michelle L, Flaherty Rebecca A, Rogers Lisa M, Gaddy Jennifer A, Aronoff David M, Manning Shannon D
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United States.
Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Front Microbiol. 2018 Nov 20;9:2786. doi: 10.3389/fmicb.2018.02786. eCollection 2018.
Macrophages play an important role in defending the host against infections by engulfing pathogens and containing them inside the phagosome, which consists of a harsh microbicidal environment. However, many pathogens have developed mechanisms to survive inside macrophages despite this challenge. Group B (GBS), a leading cause of sepsis and meningitis in neonates, is one such pathogen that survives inside macrophages by withstanding phagosomal stress. Although a few key intracellular survival factors have been identified, the mechanisms by which GBS detoxifies the phagosome are poorly defined. Transcriptional analysis during survival inside macrophages revealed strong upregulation of a putative NADH peroxidase () at 1 and 24 h post-infection. A deletion mutant of (Δ) was more susceptible to killing by a complex model of multiple phagosomal biochemical/oxidant stressors or by hydrogen peroxide alone. Moreover, compared to an isogenic wild type GBS strain, the Δ strain demonstrated impaired survival inside human macrophages and a reduced capacity to blunt macrophage reactive oxygen species (ROS) production. It is therefore likely that Npx plays a role in survival against ROS production in the macrophage. A more thorough understanding of how GBS evades the immune system through survival inside macrophages will aid in development of new therapeutic measures.
巨噬细胞在保护宿主抵御感染方面发挥着重要作用，它通过吞噬病原体并将其包裹在由恶劣的杀菌环境组成的吞噬体中来实现这一点。然而，尽管面临这一挑战，许多病原体仍已进化出在巨噬细胞内存活的机制。B族链球菌（GBS）是新生儿败血症和脑膜炎的主要病因之一，它就是这样一种通过承受吞噬体应激在巨噬细胞内存活的病原体。尽管已经确定了一些关键的细胞内存活因子，但GBS使吞噬体解毒的机制仍不清楚。对巨噬细胞内存活期间的转录分析显示，在感染后1小时和24小时，一种假定的NADH过氧化物酶（Npx）有强烈的上调。Npx的缺失突变体（ΔNpx）在多种吞噬体生化/氧化应激源的复合模型或单独使用过氧化氢处理时，更易被杀死。此外，与同基因野生型GBS菌株相比，ΔNpx菌株在人类巨噬细胞内的存活能力受损，抑制巨噬细胞活性氧（ROS）产生的能力降低。因此，Npx可能在抵抗巨噬细胞中ROS产生的存活过程中发挥作用。更深入地了解GBS如何通过在巨噬细胞内存活来逃避免疫系统，将有助于开发新的治疗措施。
