TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat
TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat
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DOI：
10.1128/iai.72.1.478-488.2004
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Badger, JL
中科院分区：
文献类型：
--
作者：
Hill, VT;Townsend, SM;Badger, JL
大肠埃希菌是新生儿细菌性败血症和脑膜炎的主要原因。我们最近发现了一种名为traj的基因，该基因有助于大肠杆菌K1穿透新生大鼠的血脑屏障。由于对疾病进展中最关键的步骤知之甚少，在自然感染途径之后，转位到肠道和扩散到淋巴组织，我们评估了traj突变导致新生大鼠全身疾病的能力。我们的研究确定，在新生大鼠中，TraJ突变体的毒力明显低于野生型，这是因为在全身疾病的早期阶段，TRAJ突变体从肠系膜淋巴传播到肝和脾深层组织以及血液的能力降低。组织病理学研究表明，虽然从感染的新生大鼠的脾和肝脏中回收的突变细菌明显较少或没有，但炎症反应比野生型定植组织的炎症反应要大得多。体外研究表明，巨噬细胞内化traj突变体的频率低于野生型，而且是通过一个不同的形态过程。此外，我们确定肝和脾内的组织巨噬细胞和树突状细胞是E.ColiK1的主要细胞靶点，并且TRAJ在这些专业吞噬细胞中显著促进了E.ColiK1的主要细胞内性质，仅在全身疾病的早期阶段。这些数据表明，与早期的迹象相反，大肠杆菌K1存在于专业吞噬细胞中，这对全身性疾病的有效进展至关重要。
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.