Porcine in vitro and in vivo models to assess the virulence of Salmonella enterica serovar Typhimurium for pigs
Porcine in vitro and in vivo models to assess the virulence of Salmonella enterica serovar Typhimurium for pigs
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DOI：
10.1258/la.2007.007084
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发表时间：
2009-01-01
影响因子：
2.4
通讯作者：
Haesebrouck, F.
中科院分区：
文献类型：
--
作者：
Boyen, F.;Pasmans, F.;Haesebrouck, F.
猪的鼠伤寒沙门氏菌感染对人类健康构成重要危害。一项有希望的控制措施是使用确定的敲除突变体开发减毒活疫苗株。优选地，应首先在允许测试大量毒株的模型中筛选候选敲除疫苗毒株的减毒作用。此后，应在猪的实验感染模型中进一步表征有限数量的选定菌株。本研究的目的是开发这样的模型。在非极化和极化猪肠上皮细胞系中评估了鼠伤寒沙门氏菌的侵袭和增殖特征。从猪血液中获得的中性粒细胞用于研究沙门氏菌抵抗这些吞噬细胞杀死的能力。在末端肠环模型中研究了诱导肠道炎症反应的能力。通过研究猪肺泡巨噬细胞和外周血单核细胞中鼠伤寒沙门氏菌的摄取和细胞内存活来模拟感染的全身阶段。这些模型应该可以筛选减毒菌株。为了进一步表征，建立了实验感染模型，提供了有关猪口腔感染过程以及定植最佳时间点（接种后第5天）和持续性（接种后第21-28天）的大量数据。总之，筛选鼠伤寒沙门氏菌菌株的毒力并随后在明确的实验感染模型中确认菌株子集将显着减少所需实验猪的数量。
Salmonella Typhimurium infections in pigs pose an important human health hazard. One promising control measure is the development of live attenuated vaccine strains using defined knockout mutants. Preferably, screening of candidate knockout vaccine strains for attenuation should first be done in models allowing testing of a large number of strains. Thereafter, a limited number of selected strains should be further characterized in an experimental infection model in pigs. The aim of the present study was to develop such models. The invasive and proliferative characteristics of S. Typhimurium were assessed in both a non-polarized and a polarized porcine intestinal epithelial cell line. Neutrophils obtained from porcine blood were used to study the capacity of Salmonella to withstand killing by these phagocytes. The ability to induce an intestinal inflammatory response was investigated in a terminal intestinal loop model. The systemic phase of infection was mimicked by studying the uptake and intracellular survival of S. Typhimurium in porcine pulmonary alveolar macrophages and peripheral blood monocytes. These models should allow screening for attenuated strains. For further characterization, an experimental infection model was established, providing extensive data on the course of an oral infection and the optimal time points for colonization (day 5 postinoculation [pi]) and persistency (days 21-28 pi) in pigs. In conclusion, screening for virulence of S. Typhimurium strains with subsequent confirmation for a subset of strains in a well-defined experimental infection model would significantly reduce the number of experimental pigs required.