Mycobacterium lepraeInfection in Monocyte-Derived Dendritic Cells and Its Influence on Antigen-Presenting Function

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Abstract
Host defense againstMycobacterium lepraeinfection is chiefly mediated by gamma interferon (IFN-γ)-secreting cytotoxic T cells. Since which antigen-presenting cell populations act to stimulate these T cells is not fully understood, we addressed the role of monocyte-derived dendritic cells (DCs). The DCs phagocytosedM. lepraeand expressed bacterially derived antigens (Ags), such as phenolic glycolipid 1 (PGL-1), in the cytoplasm, as well as on the cell surface. The expression of HLA-ABC and -DR Ags on DCs was down-regulated byM. lepraeinfection, and that of CD86 was up-regulated, but not as fully as byMycobacterium bovisBCG infection. Induction of CD83 expression required a large number ofM. lepraecells. When a multiplicity of infection of >40 was used, the DCs induced a significant proliferative and IFN-γ-producing response in autologous T cells. However, these responses were significantly lower than those induced by BCG- orMycobacterium avium-infected DCs. A CD40-mediated signaling inM. leprae-infected DCs up-regulated the expression of HLA Ags, CD86, and CD83 but did not enhance T-cell-stimulating ability. Therefore,M. leprae-infected DCs are less efficient at inducing T-cell responses. However, when the surface PGL-1 onM. leprae-infected DCs was masked by a monoclonal antibody, the DCs induced enhanced responses in both CD4+- and CD8+-T-cell subsets.M. lepraeis a unique pathogen which remains resistant to DC-mediated T-cell immunity, at least in the early stages of infection.

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