NF‐κB p65 was reported to regulate the expression of the pro‐inflammatory and antibacterial genes in macrophages.52, 53, 54 We previously demonstrated that infection with S aureus induced phosphorylation of NF‐κB p65 in macrophages, which shifted the cells into M1 phenotype and promoted the antibacterial response.38 In this study, we further revealed that SHP2 could drive M1 macrophage polarization and amplify the inflammatory response by activation of NF‐κB p65 in response to dual stimulation. Here, NFKB1 is linked to infection.