Differential Responses of Murine Bone Marrow-derived Dendritic Cells to Bacterial Components—Comparison of the Responses to Gram-positive and Gram-negative Bacterial Components—

Abstract

Although there is increasing evidence suggesting that there are fundamental differences in the host responses between Gram-positive and Gram-negative organisms, the mechanisms underlying these disparate responses remain unclear. We compared the responses of murine bone marrow-derived dendritic cells (DC) to peptidoglycan (PGN) and lipopolysaccharide (LPS), components of Gram-positive and Gram-negative bacteria, respectively. Although PGN and LPS stimulated the DCs to an equal degree, with increased MHC Class II and CD86 expressions and decreased phagocytotic activity, we demonstrated considerable differences in the functional DC maturation status : PGN stimulated the DCs to produce higher amounts of TNFα and IL-10, and to show a higher migratory response to MIP-3β as compared to LPS. PGN-stimulated DCs induced naïve T cells to produce higher amounts of Thl cytokines as compared to LPS-stimulated DCs as judged by the mixed lymphocyte reaction. Thus, it is important to develop novel therapeutic strategies for sepsis based on the pathogen-dependent inflammatory responses.