Laboratory of Infection Immunology, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India.
Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India.
Biochim Biophys Acta Gen Subj. 2020 Aug;1864(8):129627. doi: 10.1016/j.bbagen.2020.129627. Epub 2020 Apr 28.
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.
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.
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.
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.
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.
沙门氏菌的多药耐药性和高毒力的进化是由于多种宿主-病原体和非宿主环境相互作用的结果。此前，我们已经研究了沙门氏菌在不同的体外和体内环境条件下重复暴露时的适应性。本研究探讨了先前报道的传代高毒力沙门氏菌菌株高毒力的机制基础。
采用实时 PCR、流式细胞术、Western blot 和共聚焦显微镜检查高毒力菌株改变信号通路的情况。还在 Balb/c 小鼠模型系统中观察体内的高毒力。
高毒力菌株通过 NF-κB 和 Akt-NLRC4 信号通路改变 RAW-264.7 和 U-937 细胞中的细胞因子产生，从而向抗炎反应转变。与未传代的 WT-STM 相比，它们还减少了溶酶体数量，并减少了与溶酶体的共定位。在 Balb/c 小鼠中，它们还导致抗菌肽减少、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，导致器官负担增加。
高毒力沙门氏菌菌株感染通过上调 IL-10 和下调 IL-1β 表达导致抗炎环境。它们还逃避溶酶体降解以存活。抑制 NF-κB 和 Akt 信号通路后，细胞因子表达、溶酶体数量以及细菌负荷得到逆转，表明高毒力沙门氏菌菌株通过这些途径介导感染引起的免疫调节。
了解适应机制可以通过靶向细菌基因或增强宿主免疫系统来提供更好的疾病预后，这最终可能有助于控制沙门氏菌病。
