Abstract

The Far Eastern scarlet-like fever (FESLF) is the clinical-epidemic manifestation of pseudotuberculosis infection in humans is associated with a specific clonal lineage of the causative agent. Purpose of the study: to determine the pathogenetic value of the pVM82 plasmid of the FESLF causative agent, on the basis of a comparative analysis of the innate immunity cells metabolic activity and peculiarities of the inflammatory reaction during experimental infection, caused by different plasmid types of Yersinia pseudotuberculosis. Materials and Methods. The following Y. pseudotuberculosis plasmid types were used for the infection of mice: (1) H-5015 T⁺ strain (82⁺:48⁺) containing two plasmids pVM82 and pYV; (2) H-5015 T^– strain (82⁺:48^–) containing single pVM82 plasmid; (3) H-5013 T⁺ strain (48⁺) containing single pYV plasmid; (4) H-5013 T^– plasmid-free strain (82^–:48^–). Peritoneal exudate cells and samples of liver, spleen and mesenteric lymph nodes were taken from infected animals at 1, 3, 5 and 7 days post infection. The functional state of the innate immunity cells was assessed by the activity of lactate dehydrogenase (LDH) and by the level of nitric oxide (NO) metabolites. The samples of target organs were embedded in paraffin, sections were stained with hematoxylin and eosin. Results. It was found that only Y. pseudotuberculosis strains containing pVM82 plasmid had a stimulating effect the innate immunity cells. The more pronounced increase in the LDH activity, an oxygen-dependent metabolism enzyme, and the level of NO metabolites occurred in response to infection of cells with bacteria containing single pVM82 plasmid, compared with plasmid type containing additional plasmid virulence pYV. In experimental animals infected with plasmid type pYV^–: pVM82⁺ of Y. pseudotuberculosis, the disease pathology usually manifested less acute inflammation with a predominance of mononuclear cells and minor pathogen-associated destructive changes in organs. The mortality in animals infected with Y. pseudotuberculosis strains containing plasmid pVM82 (plasmid types 82⁺:48⁺ and 82⁺:48^–) was lower compared to a strain carrying only the virulence plasmid pYV (plasmid type 48⁺),—40, 30 and 80%, respectively. Conclusions. Thus, the pVM82 plasmid of Y. pseudotuberculosis determined the effective immune defense of organism, mainly through nitroxide-dependent bactericidal mechanisms of innate immunity cells. Moreover, the restriction of a generalized inflammatory reaction and induction of granulomatous inflammation were associated with this plasmid.

中文翻译：

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远东猩红热致病菌假单胞菌耶尔森氏菌pVM82质粒的致病价值

摘要

远东猩红色样发热（FESLF）是人类假结核感染的临床流行病表现，与致病因子的特定克隆谱系有关。研究目的：在比较分析不同质粒类型引起的先天免疫细胞代谢活性和实验感染过程中炎症反应的特殊性的基础上，确定FESLF病原体pVM82质粒的致病价值。耶尔森氏菌假结核。材料和方法。以下伪结核耶尔森氏菌质粒类型用于感染小鼠：（1）H-5015 T ⁺株（82 ⁺：48 ⁺）含有两个质粒pVM82和pYV；（2）含有单个pVM82质粒的H-5015 T ^–菌株（82 ⁺：48 ^–）；（3）含有单个pYV质粒的H- 5013T ⁺菌株（48 ⁺）；（4）H-5013 T ^–无质粒菌株（82 ^–：48 ^–）。在感染后1、3、5和7天从感染的动物中采集腹膜渗出液以及肝，脾和肠系膜淋巴结的样品。先天免疫细胞的功能状态通过乳酸脱氢酶（LDH）的活性和一氧化氮（NO）代谢产物的水平进行评估。将目标器官的样品包埋在石蜡中，将切片用苏木精和曙红染色。结果。发现只有假结核耶尔森氏菌含有pVM82质粒的菌株对先天免疫细胞具有刺激作用。与含有额外质粒毒力pYV的质粒类型相比，LDH活性，氧依赖性代谢酶和NO代谢物水平的增加更为明显，这是由于细胞被含有单​​个pVM82质粒的细菌感染而引起的。在感染了假结核耶尔森氏菌的质粒pYV ^–：pVM82 ⁺的实验动物中，疾病病理通常表现为较少的急性炎症，主要是单核细胞和较小的病原体相关的器官破坏性变化。在感染含有质粒pVM82的假结核耶尔森氏菌菌株（82型质粒）的动物中的死亡率⁺：48 ⁺和82 ⁺：48 ^–）比仅携带毒性质粒pYV（质粒类型48 ⁺）的菌株低，分别为40％，30％和80％。结论 因此，假结核耶尔森氏菌的pVM82质粒主要通过先天免疫细胞的氮氧化物依赖性杀菌机制来确定生物体的有效免疫防御。此外，该质粒与普遍炎症反应的限制和肉芽肿性炎症的诱导有关。