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Neurotropic Lineage III Strains of Listeria monocytogenes Disseminate to the Brain without Reaching High Titer in the Blood.
mSphere ( IF 4.8 ) Pub Date : 2020-09-16 , DOI: 10.1128/msphere.00871-20
Taylor E Senay 1 , Jessica L Ferrell 1 , Filip G Garrett 2 , Taylor M Albrecht 1 , Jooyoung Cho 1 , Katie L Alexander 1 , Tanya Myers-Morales 1 , Olivia F Grothaus 1 , Sarah E F D'Orazio 3
Affiliation  

Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bacterial growth in the blood and thus have been linked to immunocompromise. In contrast, cell-to-cell spread within nerves is thought to be mediated by a particular subset of neurotropic L. monocytogenes strains. In this study, we used a mouse model of foodborne transmission to evaluate the neurotropism of several L. monocytogenes isolates. Two strains preferentially colonized the brain stems of BALB/cByJ mice 5 days postinfection and were not detectable in blood at that time point. In contrast, infection with other strains resulted in robust systemic infection of the viscera but no dissemination to the brain. Both neurotropic strains (L2010-2198, a human rhombencephalitis isolate, and UKVDL9, a sheep brain isolate) typed as phylogenetic lineage III, the least characterized group of L. monocytogenes. Neither of these strains encodes InlF, an internalin-like protein that was recently shown to promote invasion of the blood-brain barrier. Acute neurologic deficits were observed in mice infected with the neurotropic strains, and milder symptoms persisted for up to 16 days in some animals. These results demonstrate that neurotropic L. monocytogenes strains are not restricted to any one particular lineage and suggest that the foodborne mouse model of listeriosis can be used to investigate the pathogenic mechanisms that allow L. monocytogenes to invade the brain stem.

中文翻译:

嗜神经谱系 III 单核细胞增生李斯特菌菌株传播到大脑,但血液中没有达到高滴度。

单核细胞增生李斯特菌被认为通过以下三种机制之一在大脑中定植:直接侵入血脑屏障、受感染的单核细胞穿过屏障以及轴突迁移到脑干。前两种途径似乎是在血液中细菌不受限制地生长后发生的,因此与免疫功能低下有关。相比之下,神经内的细胞间扩散被认为是由特定的嗜神经性单核细胞增生李斯特菌菌株子集介导的。在这项研究中,我们使用食源性传播的小鼠模型来评估几种单核细胞增生李斯特菌的神经性隔离。两种菌株在感染后 5 天优先定植于 BALB/cByJ 小鼠的脑干,并且在那个时间点无法在血液中检测到。相比之下,其他菌株的感染会导致内脏的强烈全身感染,但不会传播到大脑。两种嗜神经菌株(L2010-2198,一种人类菱脑炎分离物,和 UKVDL9,一种羊脑分离物)都被归类为系统发育谱系 III,这是单核细胞增生李斯特菌的特征最少的组。这些菌株均不编码 InlF,InlF 是一种类内在蛋白,最近被证明可以促进血脑屏障的侵入。在感染了嗜神经毒株的小鼠中观察到急性神经功能缺损,并且在一些动物中较轻微的症状持续长达 16 天。这些结果表明,神经营养单核细胞增生李斯特菌菌株不限于任何一种特定谱系,并表明李斯特菌病的食源性小鼠模型可用于研究允许单核细胞增生李斯特菌侵入脑干的致病机制。
更新日期:2020-09-16
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