Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Infect Immun. 2013 Nov;81(11):4013-25. doi: 10.1128/IAI.00572-13. Epub 2013 Aug 19.
Yersinia enterocolitica is a human pathogen that is ubiquitous in livestock, especially pigs. The bacteria are able to colonize the intestinal tract of a variety of mammalian hosts, but the severity of induced gut-associated diseases (yersiniosis) differs significantly between hosts. To gain more information about the individual virulence determinants that contribute to colonization and induction of immune responses in different hosts, we analyzed and compared the interactions of different human- and animal-derived isolates of serotypes O:3, O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and macrophages. The examined strains exhibited significant serotype-specific cell binding and entry characteristics, but adhesion and uptake into different host cells were not host specific and were independent of the source of the isolate. In contrast, survival and replication within macrophages and the induced proinflammatory response differed between murine, porcine, and human macrophages, suggesting a host-specific immune response. In fact, similar levels of the proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted by murine bone marrow-derived macrophages with all tested isolates, but the equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived macrophages was strongly serotype specific and considerably lower in O:3 than in O:8 strains. In addition, all tested Y. enterocolitica strains caused a considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by porcine than by murine macrophages. This could contribute to limiting the severity of the infection (in particular of serotype O:3 strains) in pigs, which are the primary reservoir of Y. enterocolitica strains pathogenic to humans.
小肠结肠炎耶尔森菌是一种普遍存在于家畜(尤其是猪)中的人类病原体。该细菌能够在多种哺乳动物宿主的肠道中定植,但在不同宿主中引起的肠道相关疾病(耶尔森菌病)的严重程度有很大差异。为了获得更多关于有助于在不同宿主中定植和诱导免疫反应的个体毒力决定因素的信息,我们分析并比较了不同血清型 O:3、O:5、27、O:8 和 O:9 的人源和动物源分离株与鼠、猪和人肠细胞和巨噬细胞的相互作用。研究的菌株表现出明显的血清型特异性细胞结合和进入特征,但黏附和摄取到不同宿主细胞不具有宿主特异性,并且与分离株的来源无关。相比之下,在巨噬细胞中的存活和复制以及诱导的促炎反应在鼠、猪和人巨噬细胞之间存在差异,表明存在宿主特异性免疫反应。事实上,所有测试的分离株都能使鼠骨髓来源的巨噬细胞分泌出相似水平的促炎细胞因子巨噬细胞炎症蛋白 2(MIP-2),但猪骨髓来源的巨噬细胞中相当于白细胞介素 8(IL-8)的反应强烈地依赖于血清型,且 O:3 菌株比 O:8 菌株的反应低得多。此外,所有测试的小肠结肠炎耶尔森菌菌株都能使猪来源的巨噬细胞分泌出更高水平的抗炎细胞因子白细胞介素 10(IL-10),这有助于限制感染的严重程度(特别是 O:3 菌株),因为猪是对人类致病的小肠结肠炎耶尔森菌菌株的主要储存宿主。