Makino Masahiko, Maeda Yumi, Kai Masanori, Tamura Toshiki, Mukai Tetsu
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
FEMS Immunol Med Microbiol. 2009 Jan;55(1):39-46. doi: 10.1111/j.1574-695X.2008.00495.x. Epub 2008 Dec 6.
The potential of Mycobacterium bovis Bacillus Calmette-Guerin (BCG) needs to be augmented to efficiently activate CD4(+) T cells through macrophages. Mycobacterium leprae-derived recombinant major membrane protein (MMP)-II induced GM-CSF production from macrophages. A recombinant BCG-SM that secretes MMP-II more efficiently produced GM-CSF and activated interferon (IFN)-gamma-producing CD4(+) T cells than did vector control BCG when infected with macrophages. The T-cell activation by BCG-SM was dependent on the GM-CSF production by macrophages. Interleukin (IL)-10 production by macrophages stimulated with M. leprae was inhibited in a GM-CSF-dependent manner when the precursor monocytes were infected with BCG-SM. BCG inducing GM-CSF production was effective in macrophage-mediated T-cell activation partially through IL-10 inhibition.
牛分枝杆菌卡介苗(BCG)的潜力需要增强,以便通过巨噬细胞有效激活CD4(+) T细胞。麻风分枝杆菌衍生的重组主要膜蛋白(MMP)-II可诱导巨噬细胞产生GM-CSF。与载体对照卡介苗相比,一种能更高效分泌MMP-II的重组卡介苗-SM(BCG-SM)在感染巨噬细胞时能产生更多GM-CSF,并激活产生干扰素(IFN)-γ的CD4(+) T细胞。BCG-SM对T细胞的激活依赖于巨噬细胞产生的GM-CSF。当用BCG-SM感染前体单核细胞时,麻风分枝杆菌刺激的巨噬细胞产生白细胞介素(IL)-10的过程以GM-CSF依赖的方式受到抑制。诱导产生GM-CSF的卡介苗在巨噬细胞介导的T细胞激活中有效,部分是通过抑制IL-10实现的。