title: A lipopeptide facilitate induction of Mycobacterium leprae killing in host cells.
abstract: Little is known of the direct microbicidal activity of T cells in leprosy, so a lipopeptide consisting of the N-terminal 13 amino acids lipopeptide (LipoK) of a 33-kD lipoprotein of Mycobacterium leprae, was synthesized. LipoK activated M. leprae infected human dendritic cells (DCs) to induce the production of IL-12. These activated DCs stimulated autologous CD4+ or CD8+ T cells towards type 1 immune response by inducing interferon-gamma secretion. T cell proliferation was also evident from the CFSE labeling of target CD4+ or CD8+ T cells. The direct microbicidal activity of T cells in the control of M. leprae multiplication is not well understood. The present study showed significant production of granulysin, granzyme B and perforin from these activated CD4+ and CD8+ T cells when stimulated with LipoK activated, M. leprae infected DCs. Assessment of the viability of M. leprae in DCs indicated LipoK mediated T cell-dependent killing of M. leprae. Remarkably, granulysin as well as granzyme B could directly kill M. leprae in vitro. Our results provide evidence that LipoK could facilitate M. leprae killing through the production of effector molecules granulysin and granzyme B in T cells.
authors: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan. yumi@nih.go.jp
authors: Yumi
authors: Y
authors: Maeda
authors: Toshiki
authors: T
authors: Tamura
authors: Yasuo
authors: Y
authors: Fukutomi
authors: Tetsu
authors: T
authors: Mukai
authors: Masanori
authors: M
authors: Kai
authors: Masahiko
authors: M
authors: Makino
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D055666:Lipopeptides / Q000276:immunology*; D050296:Microbial Viability; D009166:Mycobacterium leprae / Q000276:immunology* / Q000502:physiology*; D054353:Perforin / Q000096:biosynthesis
chemical_list: D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; D055666:Lipopeptides; D054353:Perforin; D018664:Interleukin-12; D007371:Interferon-gamma; D053804:Granzymes