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Immune modulations and survival strategies of evolved hypervirulent Salmonella Typhimurium strains.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2020-04-28 , DOI: 10.1016/j.bbagen.2020.129627
Diana Pradhan 1 , Jasmin Pradhan 1 , Abtar Mishra 2 , Kapudeep Karmakar 3 , Rohan Dhiman 2 , Dipshikha Chakravortty 4 , Vidya Devi Negi 1
Affiliation  

BACKGROUND Evolving multidrug-resistance and hypervirulence in Salmonella is due to multiple host-pathogen, and non-host environmental interactions. Previously we had studied Salmonella adaptation upon repeated exposure in different in-vitro and in-vivo environmental conditions. This study deals with the mechanistic basis of hypervirulence of the passaged hypervirulent Salmonella strains reported previously. METHODS Real-time PCR, flow cytometry, western blotting, and confocal microscopy were employed to check the alteration of signaling pathways by the hypervirulent strains. The hypervirulence was also looked in-vivo in the Balb/c murine model system. RESULTS The hypervirulent strains altered cytokine production towards anti-inflammatory response via NF-κB and Akt-NLRC4 signaling in RAW-264.7 and U-937 cells. They also impaired lysosome number, as well as co-localization with the lysosome as compared to unpassaged WT-STM. In Balb/c mice also they caused decreased antimicrobial peptides, reduced nitric oxide level, altered cytokine production, and reduced CD4+ T cell population leading to increased organ burden. CONCLUSIONS Hypervirulent Salmonella strains infection resulted in an anti-inflammatory environment by upregulating IL-10 and down-regulating IL-1β expression. They also evaded lysosomal degradation for their survival. With inhibition of NF-κB and Akt signaling, cytokine expression, lysosome number, as well as the bacterial burden was reverted, indicating the infection mediated immune modulation by the hypervirulent Salmonella strains through these pathways. GENERAL SIGNIFICANCE Understanding the mechanism of adaptation can provide better disease prognosis by either targeting the bacterial gene or by strengthening the host immune system that might ultimately help in controlling salmonellosis.

中文翻译:

进化性高毒鼠伤寒沙门氏菌菌株的免疫调节和生存策略。

背景技术沙门氏菌中发展的多药耐药性和高毒力是由于多种宿主-病原体和非宿主环境的相互作用。以前,我们已经研究了在不同的体外和体内环境条件下反复接触沙门氏菌的适应性。该研究涉及先前报道的传代高毒沙门氏菌菌株高毒力的机理基础。方法采用实时荧光定量PCR,流式细胞仪,免疫印迹和共聚焦显微镜检查高毒力菌株对信号通路的改变。还可以在Balb / c鼠模型系统中体内观察高毒力。结果高毒力菌株通过RAW-264.7和U-937细胞中的NF-κB和Akt-NLRC4信号转导了抗炎反应的细胞因子产生。他们还损害了溶酶体的数量,以及与未通过WT-STM相比与溶酶体共定位。在Balb / c小鼠中,它们还引起抗菌肽减少,一氧化氮水平降低,细胞因子产生改变以及CD4 + T细胞数量减少,从而导致器官负担增加。结论高毒性沙门氏菌菌株感染通过上调IL-10和下调IL-1β表达而产生抗炎环境。他们还逃避了溶酶体降解的生存。通过抑制NF-κB和Akt信号传导,细胞因子的表达,溶酶体数目以及细菌负荷得以恢复,这表明高毒力沙门氏菌菌株通过这些途径介导了感染介导的免疫调节。
更新日期:2020-04-28
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