Virulence Factors FimA of Porphyromonas gingivalis Promotes MHC-Ⅱ Degradation through Autophagy Mediated by P62

DU Ruoqi; ZHANG Xiusen; ZHANG Xudong; FU Gailing

doi:10.15926/j.cnki.issn2096-7381.2025.02.002

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.