This study suggests that Rv1768 interacts with S100A9/A8 to suppress both the NF-κB-TNF-α signaling pathway during the early infection stage (about 4 h) and the metabolism of arachidonic acid at the late infection stage (after 12 h) to promote the intracellular survival of mycobacteria, and that disturbing the interaction between Rv1768 and S100A9/S100A8 may be a potential therapeutic target in TB. Here, NFKB1 is linked to tuberculosis.