Mycobacterium leprae infection in monocyte-derived dendritic cells and its influence on antigen-presenting function.
Host defense against Mycobacterium leprae infection is chiefly mediated by gamma interferon (IFN-gamma)-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 phagocytosed M. leprae and 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 by M. leprae infection, and that of CD86 was up-regulated, but not as fully as by Mycobacterium bovis BCG infection. Induction of CD83 expression required a large number of M. leprae cells. When a multiplicity of infection of >40 was used, the DCs induced a significant proliferative and IFN-gamma-producing response in autologous T cells. However, these responses were significantly lower than those induced by BCG- or Mycobacterium avium-infected DCs. A CD40-mediated signaling in M. 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 on M. leprae-infected DCs was masked by a monoclonal antibody, the DCs induced enhanced responses in both CD4(+)- and CD8(+)-T-cell subsets. M. leprae is a unique pathogen which remains resistant to DC-mediated T-cell immunity, at least in the early stages of infection.
Hashimoto
Ken
K
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan.
Maeda
Yumi
Y
Kimura
Hiroaki
H
Suzuki
Koichi
K
Masuda
Akihiro
A
Matsuoka
Masanori
M
Makino
Masahiko
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D006017:Glycolipids / Q000037:antagonists & inhibitors / Q000276:immunology; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology; D000097802:CD83 Antigen
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D015703:Antigens, CD; D051940:B7-2 Antigen; D006017:Glycolipids; D006680:HLA Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C497964:CD86 protein, human; C045169:phenolic glycolipid I, Mycobacterium leprae