Myeloid differentiation primary response protein 88 (MyD88)-deficient dendritic cells exhibit a skewed cytokine response to BCG

Abstract

Objective: Macrophages and dendritic cells (DCs) play key role in the recognition of mycobacterial infection and mounting of antimycobacterial immunity. In case of macrophages, recognition of BCG and other mycobacteria has been attributed predominantly to MyD88-dependent singling. Interestingly, in previous study with bone marrow-derived DCs, we have shown that BCG promotes the survival of wild-type and MyD88 -/- cells to the comparable levels. In the present study, we further examined MyD88 -/- DC's response to BCG. Results: Bone marrow-derived DCs from wild-type and MyD88 -/- mice were stimulated with BCG and analyzed for cytokine secretion. As expected, BCG-stimulated wild-type DCs produced significant amount of TNF-α and IL-12p40 in response to BCG. Interestingly, BCG-stimulated MyD88 -/- DCs were also found to secret significantly higher levels of TNF-α and IL-12p40, compared with unstimulated DCs. We further observed that wild-type DCs produced significant level of immunosuppressive cytokine IL-10 in response to BCG, whereas MyD88 -/- DCs secreted very low amount of IL-10 when stimulated with BCG. These findings demonstrated that MyD88 -/- DCs exhibit a skewed cytokine response to BCG.