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利用多种机制从肠固有层扩散至肠系膜淋巴结。

use multiple mechanisms to disseminate from the intestinal lamina propria to the mesenteric lymph nodes.

作者信息

Nowacki Joshua S, Jones Grant S, D'Orazio Sarah E F

机构信息

Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA.

出版信息

Microbiol Spectr. 2025 Feb 4;13(2):e0259524. doi: 10.1128/spectrum.02595-24. Epub 2024 Dec 23.

Abstract

UNLABELLED

are facultative intracellular bacterial pathogens that cause foodborne disease in humans. The bacteria can use the surface protein InlA to invade intestinal epithelial cells or transcytose across M cells in the gut, but it is not well understood how the bacteria traffic from the underlying lamina propria to the draining mesenteric lymph nodes (MLN). Previous studies indicated that associated with both monocytes and dendritic cells in the intestinal lamina propria. We show here that CCR2 mice had a significant reduction in Ly6C monocytes in the MLN but no change in bacterial burden following foodborne infection; thus, dissemination of associated with monocytes is not required for colonization of the MLN. To block CCR7-mediated trafficking of dendritic cells from the lamina propria, we treated mice with anti-VEGFR3 antibody (clone AFL4) prior to and during infection but did not see a change in dendritic numbers in the MLN as had been previously reported with other anti-VEGFR3-specific antibodies. However, increasing the number of circulating dendritic cells by treating mice with rFlt3L resulted in a significant increase in in the lymph nodes that drain the small intestine and the spleen. Whole-mount fluorescent microscopy of lymphatic vessels following ligated loop infection revealed both free-floating and cell-associated bacteria within lymphatic vessels. Together, these results suggest that can use multiple, redundant mechanisms to disseminate from the gut tissue to the MLN.

IMPORTANCE

Consumption of the foodborne bacterial pathogen results in a wide spectrum of human disease from mild self-limiting gastroenteritis to life-threatening infections of the bloodstream, brain, and placenta. It is not well understood how the bacteria migrate from the intestines to the draining mesenteric lymph nodes, which are thought to serve as the last barrier to prevent systemic infections. Results presented here reveal multiple redundant mechanisms can use to disseminate from the ileum or colon to the mesenteric lymph nodes.

摘要

未标记

是兼性细胞内细菌病原体,可导致人类食源性疾病。该细菌可利用表面蛋白InlA侵入肠道上皮细胞或穿过肠道中的M细胞进行跨细胞转运,但目前尚不清楚该细菌如何从下层固有层转移至引流肠系膜淋巴结(MLN)。先前的研究表明,其与肠道固有层中的单核细胞和树突状细胞均有关联。我们在此表明,CCR2基因敲除小鼠的MLN中Ly6C单核细胞显著减少,但食源性感染后细菌载量未发生变化;因此,MLN定植并不需要与单核细胞相关的扩散。为了阻断CCR7介导的树突状细胞从固有层的转运,我们在感染前和感染期间用抗VEGFR3抗体(克隆AFL4)处理小鼠,但未观察到MLN中树突状细胞数量发生变化,而此前使用其他抗VEGFR3特异性抗体时曾有过相关报道。然而,用重组Flt3L处理小鼠以增加循环树突状细胞数量,导致小肠和脾脏引流淋巴结中的显著增加。结扎环感染后对淋巴管进行全组织荧光显微镜检查发现,淋巴管内既有游离的细菌,也有与细胞相关的细菌。总之,这些结果表明,可利用多种冗余机制从肠道组织扩散至MLN。

重要性

食源性细菌病原体的摄入会导致从轻度自限性肠胃炎到威胁生命的血液、大脑和胎盘感染等广泛的人类疾病。目前尚不清楚该细菌如何从肠道迁移至引流肠系膜淋巴结,而肠系膜淋巴结被认为是预防全身感染的最后一道屏障。此处呈现的结果揭示了可用于从回肠或结肠扩散至肠系膜淋巴结的多种冗余机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/488e/11792513/00733a811bf7/spectrum.02595-24.f001.jpg

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