食管疾病2025，Vol.7Issue(2)：88-93,6.DOI:10.15926/j.cnki.issn2096-7381.2025.02.002
牙龈卟啉单胞菌FimA通过P62介导的自噬促进MHC-Ⅱ的降解
Virulence Factors FimA of Porphyromonas gingivalis Promotes MHC-Ⅱ Degradation through Autophagy Mediated by P62
摘要
Abstract
Objective To investigate the effect of Porphyromonas gingivalis(Pg)infection on MHC-Ⅱin esophageal squamous cell carcinoma(ESCC)and its immune regulation mechanism.Methods The expression level of MHC-Ⅱand the infiltration of CD8+T cells in different treatment groups were detected by tissue immunofluorescence.The colocalization of P62,FimA(the main virulence factor flagellin),Lamp1(lysosome-associated membrane protein 1)and MHC-Ⅱin each group was observed by immunofluorescence staining.The expression levels of P62 and MHC-Ⅱ in KYSE150 cells infected by Pg were detected by Western blot.Expressions of Granzyme B and Perforin were detected by flow cytometry when Pg-positive KYSE150 was co-cultured with peripheral blood mononuclear cells(PBMCs).Results Immunofluorescence showed a significant reduction in MHC-Ⅱexpression in Pg-positive tissues compared to Pg-negative tissues,accompanied with a significant reduction in T cell infiltration.The co-localization of P62,FimA and Lamp1 was weakened in 2-BP(palmitoyltransferase inhibitor)group and sh-ZDHHC8(transfected with lentiviral plasmid knockdown ZDHHC8)group compared with the Pg infection group alone.The co-localization of P62,FimA and MHC-Ⅱwas weakened in P62 knockdown group compared with Pg infection group alone.Western blot showed that the expression of MHC-Ⅱwas decreased after Pg infection of KYSE150 cells,and the expression of MHC-Ⅱcould be restored after P62 knockdown.The results of flow cytometry showed that the expression of cytotoxic molecules on the surface of CD8+T cells was significantly reduced in the Pg infected group(Gzmb,Perforin),while partial expression was restored in the 2BP group,shP62 group,and chloroquine(CQ)group.Conclusion FimA may activate P62 mediated autophagy through palmitoylation,recruit MHC-Ⅱ to lysosomal degradation,inhibit T cell immune response,and participate in immunosuppression and tumor progression.关键词
食管鳞状细胞癌/牙龈卟啉单胞菌/自噬Key words
esophageal squamous cell carcinoma/Porphyromonas gingivalis/autophagy分类
临床医学引用本文复制引用
杜若琪,张秀森,张旭东,付改玲..牙龈卟啉单胞菌FimA通过P62介导的自噬促进MHC-Ⅱ的降解[J].食管疾病,2025,7(2):88-93,6.基金项目
国家自然科学基金面上项目(82073029)河南省自然科学基金项目(242102310146) （82073029）
