Bacterial infection induces expression of functional MHC class II molecules in murine and human osteoblasts

A growing body of evidence has shown that bacterially challenged osteoblasts can play a significant role in the initiation of inflammatory immune responses at sites of bone disease. We have recently demonstrated the surprising ability of osteoblasts exposed to bacteria to express CD40, a molecule that plays a critical costimulatory role in the activation of T lymphocytes. In the present study, we have extended our investigations into the ability of osteoblasts to interact with CD4+ T lymphocytes by determining the expression of antigen-presenting major histocompatibility complex (MHC) class II molecules in murine and human osteoblasts following exposure to two common pathogens of bone, Staphylococcus aureus and Salmonella. Cultured osteoblasts were found to respond rapidly to bacterial challenge by induction of mRNA encoding MHC class II molecules or its transcriptional regulator. Increased mRNA expression translated into expression of MHC class II proteins in murine and human osteoblasts as determined by Western blot analysis and by immunohistochemical and immunofluorescent microscopy. Furthermore, the increased surface expression of these molecules on osteoblasts exposed to bacteria was confirmed by FACS analysis. Finally, we show that bacterial challenge results in the elevated functional expression of MHC class II molecules on osteoblasts by demonstrating the enhanced ability of these cells to interact with T lymphocytes and to initiate antigen-specific T cell activation. Taken together, these data suggest a previously unappreciated role for osteoblasts in the initiation of T lymphocyte activation at sites of bacterial infection in bone tissue.