Streptococcus aureus infection of mouse or human osteoblasts induces high levels of interleukin-6 and interleukin-12 production

Staphylococcus aureus is the principal causative agent of the inflammatory bone disease osteomyelitis. Unfortunately, the pathogenesis of this often c hronic infection is poorly understood and is complicated by the recent obse rvation that bone-forming osteoblasts can harbor S. aureus. Such an infecti on presents a significant challenge for the host immune response, because o steoblasts are not known to initiate protective cell-mediated immune respon ses. Cultured mouse and human osteoblasts infected with S. aureus were foun d to express high levels of interleukin (IL)-6 and IL-12p75, on the basis o f complementary investigations demonstrating both S. aureus-induced up-regu lation of expression of IL-6 and IL-12p40 mRNA and secretion of IL-6 and IL -12p75 by these cells. Additionally, a quantitative bioassay demonstrated t hat IL-12p75 secreted after infection was biologically active. These studie s are the first to demonstrate induced IL-12p75 expression by osteoblasts a nd suggest a previously unrecognized role for osteoblasts in initiating imm une responses after S. aureus infection.