Here, we show that an anti-IsdB mAb can facilitate S. aureus internalization and survival in macrophages in vitro and mediate S. aureus dissemination in a murine model of implant-associated osteomyelitis via a multimolecular complex that includes Spa, the anti-IsdB mAb, IsdB, Hb-Hp, and CD163. This evidence concerns the gene CD163 and osteomyelitis.