摘要

Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells.We characterized in vivo interactions between group A streptococci (GAS) and cells involved in innate immune responses, using human biopsies (n = 70) collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria.This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections highlights a need for alternative therapeutic strategies.

译文

A 组链球菌严重软组织感染,如坏死性筋膜炎,是与高死亡率相关的快速进行性感染。A 组链球菌通常被认为是一种细胞外病原体,但已被证明存在于宿主细胞内。我们使用从 17 名软组织感染患者中收集的人体活检 (n = 70),表征了 A 组链球菌 (GAS) 和参与先天免疫反应的细胞之间的体内相互作用。免疫染色和原位图像分析显示活组织检查中有大量细菌,即使是在长期抗生素治疗后收集的活组织检查中。通过使用细菌活性染色来评估链球菌的活性,该染色在 74% 的活检中显示了活菌。气体存在于吞噬细胞内的细胞外和细胞内,主要存在于巨噬细胞内。细胞内气体主要出现在新感染组织的活检中,其特征是炎症和细菌载量较低,而在严重发炎的组织中,纯细胞外气体或细胞内和细胞外气体的组合占主导地位。后者组织也与半胱氨酸蛋白酶的显著增加有关,链球菌的发热外毒素 SpeB。体外研究证实巨噬细胞是活气体的储存库, 与野生型细菌相比,感染 speB 缺失突变体后产生的活气体细胞频率显著降低。这是第一项证明 GAS 在急性侵入性感染期间在巨噬细胞内存活的研究。这种细胞内存在可能已经演变为一种避免抗生素根除的机制,这可能解释了我们的发现,即即使在长期静脉注射抗生素治疗后收集的组织中也存在高细菌负荷。对链球菌软组织感染发病机制的新认识凸显了对替代治疗策略的需求。

macrophages

免疫 巨噬细胞 临床研究术语
概述  :  

巨噬细胞是免疫系统重要成分之一,存在于组织中的免疫细胞,最早由Mechnikov在1884年发现,是一种广泛分布于全身血液、组织的免疫细胞。巨噬细胞能够吞噬和杀灭胞内寄生虫、细菌、肿瘤细胞以及自身衰老和异常细胞,在机体的免疫防御、免疫自稳和免疫监视中发挥重要作用。巨噬细胞组织分布多样性和异质性的特点,使之一直以来都是科研工作者们热门研究对象。   分型 巨噬细胞的分类目前还没有统一标准,比较熟悉的分类主要为发挥促炎效应的M1型巨噬细

macrophages   美[’mækroʊ,feidʒiz]

释    义    n.巨噬细胞

例    句    They are reported to serve as biological response modifiers with the capability to activate macrophages and T-cells, and to produce cytokines, interleukins and tumor necrosis factors.据报道,它们可以作为生物反应调节剂,激活巨噬细胞和t细胞,并产生细胞因子、白细胞介素和肿瘤坏死因子。

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