沙门菌SptP调控巨噬细胞MAPK-CDK6-RB通路的初步分析

doi:10.11843/j.issn.0366-6964.2023.03.030

摘要/Abstract

摘要： 本研究旨在探讨沙门菌毒力因子SptP对猪巨噬细胞MAPK-CDK6-RB通路及外陷网(METs)形成的影响。首先比较Salmonella 13312(猪霍乱沙门菌)和Salmonella 14028(鼠伤寒沙门菌)、Salmonella 13314(亚利桑那沙门菌)诱导的METs水平的差异，然后生物信息学预测参与METs调控的沙门菌基因，最后采用ChIP和MALDI-TOF试验进行验证。结果表明，Salmonella 13312和Salmonella 14028诱导的METs水平显著低于Salmonella 13314(P<0.05)，提示沙门菌基因可能通过某种途径调控METs释放的某些关键步骤。Domain—Domain相互作用生物信息学预测结合ChIP、MALDI-TOF试验验证表明沙门菌基因SptP参与了该过程，其作用的宿主靶分子可能为MAPK通路下游基因ABL1和CDK6，SptP可能通过调节ABL1和CDK6的去磷酸化而参与MAPK-CDK6-RB通路的调控，该通路可能与METs的生成有关。SptP-MAPK-CDK6-RB通路可能是沙门菌逃避宿主免疫系统的重要途径，该研究结果为沙门菌逃避宿主免疫造成仔猪感染和长期携带机制的研究提供了新的见解。

关键词: 沙门菌, SptP, 细胞外陷网, 巨噬细胞, MAPK, ABL1

Abstract: The purpose of this study was to explore the effect of Salmonella virulence factor SptP on MAPK-CDK6-RB pathway and the formation of macrophage extracellular traps (METs). Firstly, compare the difference of METs levels induced by Salmonella 13312 (Salmonella Choleraesuis), Salmonella 14028 (Salmonella Typhimurium) and Salmonella 13314 (Salmonella Arizona). Then, predict the Salmonella genes involved in the regulation of METs using bioinformatics method. Finally, verify the result using ChIP and MALDI-TOF experiments. The results showed that the levels of METs induced by Salmonella 13312 and Salmonella 14028 were significantly lower than Salmonella 13314 (P<0.05), suggested that Salmonella genes may regulate some key steps of the biogenesis of METs through a certain pathway. The bioinformatics prediction of Domain—Domain interaction combined with ChIP and MALDI-TOF experiments showed that the Salmonella gene SptP participated in this process, and its host target molecules may be the downstream genes, ABL1 and CDK6, of MAPK pathway. SptP may participate in the regulation of MAPK-CDK6-RB pathway by regulating the dephosphorylation of ABL1 and CDK6, this pathway may responsible for the biogenesis of METs. The results suggest that SptP-MAPK-CDK6-RB pathway may be an important pathway for Salmonella to escape the host immune system. The discovery of this pathway provides new insights for the study of the mechanism of infection and long-term carrier of Salmonella to escape the host immune system.

Key words: Salmonella, SptP, extracellular traps, macrophages, MAPK, ABL1

中图分类号:

S855.1

姚敏, 石博妹, 黄廷华. 沙门菌SptP调控巨噬细胞MAPK-CDK6-RB通路的初步分析[J]. 畜牧兽医学报, 2023, 54(3): 1187-1198.

YAO Min, SHI Bomei, HUANG Tinghua. A Preliminary Research of the Regulation of MAPK-CDK6-RB Pathway by Salmonella SptP in Macrophages[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 1187-1198.

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