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由分泌麻风分枝杆菌主要膜蛋白-II的重组卡介苗感染的巨噬细胞介导的GM-CSF依赖性T细胞活化。

GM-CSF-mediated T-cell activation by macrophages infected with recombinant BCG that secretes major membrane protein-II of Mycobacterium leprae.

作者信息

Makino Masahiko, Maeda Yumi, Kai Masanori, Tamura Toshiki, Mukai Tetsu

机构信息

Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

出版信息

FEMS Immunol Med Microbiol. 2009 Jan;55(1):39-46. doi: 10.1111/j.1574-695X.2008.00495.x. Epub 2008 Dec 6.

Abstract

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.

摘要

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。

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