Through RNA-Seq and GSEA analysis, we identified that F. nucleatum infection markedly upregulates several signaling pathways associated with inflammation and tumor progression, notably key genes in the NF-κB pathway, including Nfkb1, Nfkb2, Tnf, and Malt1. Subsequent RT-qPCR and Western Blot analyses confirmed a significant increase in the expression levels of P50 and P100 proteins following infection, which suggests that the NF-κB pathway is crucial in regulating M2-type polarization induced by F. nucleatus infection. The gene discussed is CD40; the disease is infection.