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TraJ-Dependent Escherichia coli K1 Interactions with Professional Phagocytes Are Important for Early Systemic Dissemination of Infection in the Neonatal Rat

机译:依赖TraJ的大肠杆菌K1与专业吞噬细胞的相互作用对新生大鼠感染的早期系统传播很重要。

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Escherichia coli is a major cause of neonatal bacterial sepsis and meningitis. We recently identified a gene, traJ, which contributes to the ability of E. coli K1 to penetrate the blood-brain barrier in the neonatal rat. Because very little is known regarding the most critical step in disease progression, translocation to the gut and dissemination to the lymphoid tissues after a natural route of infection, we assessed the ability of a traJ mutant to cause systemic disease in the neonatal rat. Our studies determined that the traJ mutant is significantly less virulent than the wild type in the neonatal rat due to a decreased ability to disseminate from the mesenteric lymph nodes to the deeper tissues of the liver and spleen and to the blood during the early stages of systemic disease. Histopathologic studies determined that although significantly less or no mutant bacteria were recovered from the spleen and livers of infected neonatal rats, the inflammatory response was considerably greater than that in wild-type-colonized tissues. In vitro studies revealed that macrophages internalize the traJ mutant less frequently than they do the wild type and by a morphologically distinct process. Furthermore, we determined that tissue macrophages and dendritic cells within the liver and spleen are the major cellular targets of E. coli K1 and that TraJ significantly contributes to the predominantly intracellular nature of E. coli K1 within these professional phagocytes exclusively during the early stages of systemic disease. These data indicate that, contrary to earlier indications, E. coli K1 resides within professional phagocytes, and this is essential for the efficient progression of systemic disease.
机译:大肠杆菌是新生儿细菌性败血症和脑膜炎的主要原因。我们最近鉴定了一个基因 traJ ,该基因有助于 E的功能。大肠杆菌K1穿透新生大鼠的血脑屏障。由于对自然疾病感染后疾病进展,肠道易位和淋巴组织扩散的最关键步骤知之甚少,我们评估了 traJ 突变体引起全身性疾病的能力在新生大鼠中。我们的研究确定, traJ 突变体在新生大鼠中的毒性远低于野生型,这是由于从肠系膜淋巴结向肝脏和脾脏的较深组织以及向淋巴结转移的能力降低了。全身疾病早期的血液。组织病理学研究确定,尽管从感染的新生大鼠的脾脏和肝脏中回收的细菌少得多或没有,但其炎症反应比野生型定殖组织的炎症反应大得多。体外研究表明,巨噬细胞将 traJ 突变体内在化的频率低于野生型,并且是通过形态学上独特的过程。此外,我们确定肝脏和脾脏内的组织巨噬细胞和树突状细胞是 E的主要细胞靶标。大肠杆菌 K1和TraJ显着促进了 E的主要细胞内特性。这些专业吞噬细胞中的大肠杆菌K1仅在系统性疾病的早期出现。这些数据表明,与以前的说法相反, E。大肠杆菌K1驻留在专业吞噬细胞中,这对于有效地发展全身性疾病至关重要。

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