Salmonella enterica is a veterinary and zoonotic pathogen of global importance. While murine and cell-based models of infection have provided considerable knowledge about the molecular basis of virulence of Salmonella, relatively little is known about salmonellosis in naturally-affected large animal hosts such as cattle, which are a reservoir of human salmonellosis. As in humans, Salmonella causes bovine disease ranging from self-limiting enteritis to systemic typhoid-like disease and exerts significant economic and welfare costs. Understanding the nature and consequences of Salmonella interactions with bovine cells will inform the design of effective vaccines and interventions to control animal and zoonotic infections. In calves challenged orally with S. Dublin expressing green fluorescent protein (GFP) we observed that the bacteria were predominantly extracellular in the distal ileal mucosa and within gut-associated lymph nodes 48 h post-infection. Intracellular bacteria, identified by flow cytometry using the GFP signal, were predominantly within MHCII+ macrophage-like cells. In contrast to observations from murine models, these S. Dublin-infected cells had elevated levels of MHCII and CD40 compared to both uninfected cells from the same tissue and cells from the cognate tissue of uninfected animals. Moreover, no gross changes of the architecture of infected lymph nodes were observed as was described previously in a mouse model. In order to further investigate Salmonella-macrophage interactions, net replication of S. enterica serovars that differ in virulence in cattle was measured in bovine blood-derived macrophages by enumeration of gentamicin-protected bacteria and fluorescence dilution, but did not correlate with host-specificity.

中文翻译：

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肠沙门氏菌血清都柏林与牛宿主细胞相互作用的性质和后果

肠炎沙门氏菌是具有全球重要性的兽医和人畜共患病原体。虽然鼠类和基于细胞的感染模型已经提供了有关沙门氏菌毒力分子基础的大量知识，但对受自然影响的大型动物宿主（如牛）中沙门氏菌病的了解相对较少，牛是人沙门氏菌病的宿主。与人类一样，沙门氏菌会引起从自限性肠炎到全身性伤寒样疾病的牛疾病，并造成巨大的经济和福利成本。了解沙门氏菌与牛细胞相互作用的性质和后果，将有助于设计有效的疫苗和干预措施，以控制动物和人畜共患病感染。在小牛中口服S挑战。都柏林表达绿色荧光蛋白（GFP），我们观察到细菌在感染后48小时主要位于回肠远端粘膜和肠道相关淋巴结内的细胞外。通过使用GFP信号通过流式细胞术鉴定的细胞内细菌主要存在于MHCII +巨噬细胞样细胞内。与从鼠类模型中观察到的结果相反，与来自相同组织的未感染细胞和来自未感染动物的同源组织的细胞相比，这些感染了都柏林链球菌的细胞的MHCII和CD40水平升高。而且，没有观察到感染的淋巴结结构的总体变化，如先前在小鼠模型中所述。为了进一步研究沙门氏菌-巨噬细胞的相互作用，S的净复制。