Essential role of Salmonella Enteritidis DNA adenine methylase in modulating inflammasome activation

BMC Microbiology

article

Guo, Yaxin¹  Jiao, Xinan¹  Pan, Zhiming¹  Gu, Dan¹  Huang, Tingting¹  Cao, Liyan¹  Zhu, Xinyu¹  Zhou, Yi¹  Wang, Kangru¹  Kang, Xilong¹  Meng, Chuang¹ 

[1] Jiangsu Key Laboratory of Zoonosis, Yangzhou University;Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University;Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of A griculture of China, Yangzhou University;Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University

关键词: Salmonella Enteritidis;    DNA adenine methylase;    Inflammasome;    Cytotoxicity;    Caspase-1;    Interleukin-1β;   

DOI  :  10.1186/s12866-020-01919-z

学科分类：放射科、核医学、医学影像

来源: BioMed Central

【 摘 要 】

Salmonella Enteritidis (SE) is one of the major foodborne zoonotic pathogens of worldwide importance which can induce activation of NLRC4 and NLRP3 inflammasomes during infection. Given that the inflammasomes play an essential role in resisting bacterial infection, Salmonella has evolved various strategies to regulate activation of the inflammasome, most of which largely remain unclear. A transposon mutant library in SE strain C50336 was screened for the identification of the potential factors that regulate inflammasome activation. We found that T3SS-associated genes invC, prgH, and spaN were required for inflammasome activation in vitro. Interestingly, C50336 strains with deletion or overexpression of Dam were both defective in activation of caspase-1, secretion of IL-1β and phosphorylation of c-Jun N-terminal kinase (Jnk). Transcriptome sequencing (RNA-seq) results showed that most of the differentially expressed genes and enriched KEGG pathways between the C50336-VS-C50336Δdam and C50336-VS-C50336::dam groups overlapped, which includes multiple signaling pathways related to the inflammasome. C50336Δdam and C50336::dam were both found to be defective in suppressing the expression of several anti-inflammasome factors. Moreover, overexpression of Dam in macrophages by lentiviral infection could specifically enhance the activation of NLRP3 inflammasome independently via promoting the Jnk pathway. These data indicated that Dam was essential for modulating inflammasome activation during SE infection, there were complex and dynamic interplays between Dam and the inflammasome under different conditions. New insights were provided about the battle between SE and host innate immunological mechanisms.

【 授权许可】

CC BY|CC0