A lipopeptide facilitate induction of Mycobacterium leprae killing in host cells.

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 pr...

Full description

Bibliographic Details
Published in:PLoS Neglected Tropical Diseases
Main Authors: Yumi Maeda, Toshiki Tamura, Yasuo Fukutomi, Tetsu Mukai, Masanori Kai, Masahiko Makino
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2011
Subjects:
Online Access:https://doi.org/10.1371/journal.pntd.0001401
https://doaj.org/article/54b80051cdb74e6db95a50dfcc07424d
Description
Summary: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.