ObjectiveThis study aimed to explore the functions and potential regulatory targets of local macrophages in nonalcoholic fatty liver combined withPorphyromonas gingivalis(P. gingivalis)infection.MethodsSingle-cell RNA sequencing was used to analyze the phenotypes and functional changes in various cells in the liver tissue of nonalcoholic steatohepatitis (NASH) mice fed withP. gingivalis. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and immunofluorescence staining were applied to observe the inflammation and expression levels of macrophage antigen presenting functional markers in the NASH liver. Oil red staining was performed to observe the accumulation of local adipose tissue in the NASH liver. Results were verified through RT-PCRand RNA sequencing usingP. gingivalis-lipopolysaccharide treated mouse peritoneal macrophages.ResultsIn comparison with healthy livers with Kupffer cells, the NASH liver combined withP. gingivalisinfection-related macrophages showed significant heterogeneity. C1qb, C1qc, Mafb, Apoe, and Cd14 were highly expressed, but Cd209a, H2-Aa, H2-Ab1, and H2-DMb1, which are related to the antigen presentation function, were weakly expressed. Furtherin vivoandin vitroinvestigations indicated that the activation and infiltration of these macrophages may be due to localP. gingivalis-lipopolysaccharide accumulation.ConclusionP. gingivalis-lipopolysaccharide induces a local macrophage immunotolerance phenotype in nonalcoholic fatty liver, which may be the key mechanism of periodontitis pathogen infection that promotes NASH inflammation and pathogenesis. This study further clarifies the dysfunction and regulatory mechanisms of macrophages in the pathogenesis ofP. gingivalis-infected NASH, thereby providing potential therapeutic targets for its clinical treatment.
