Maeda Yumi, Mukai Tetsu, Spencer John, Makino Masahiko
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan.
Infect Immun. 2005 May;73(5):2744-50. doi: 10.1128/IAI.73.5.2744-2750.2005.
A search for an immunomodulating agent from mycobacteria was carried out using Mycobacterium leprae. The antigenicity of each fraction of the bacterial membrane, which contains the most antigenic components of M. leprae, was assessed by using sera from paucibacillary leprosy. N-terminal sequencing of the serum-reactive protein and functional assessment of the membrane fractions using monocyte-derived dendritic cells (DCs) identified major membrane protein II (MMP-II) as one of the efficient T-cell-activating candidates. Purified MMP-II stimulated DCs from healthy individuals to produce interleukin-12 p70 and up-regulated the surface expression of major histocompatibility complex class I and II, CD86, and CD83 molecules. Also, there was an increase in the percentage of CD83(+) cells in the DC population. Furthermore, MMP-II-pulsed DCs expressed their derivatives on their surfaces. Using Toll-like receptor 2 (TLR-2)-dependent receptor constructs, we found that TLR-2 signaling was involved in DC maturation induced by MMP-II. Taken together, MMP-II can be recognized as an immunomodulating protein in terms of activation of antigen-presenting cells and innate immunity.
利用麻风分枝杆菌开展了从分枝杆菌中寻找免疫调节剂的研究。通过使用少菌型麻风患者的血清，评估了细菌膜各组分（其中包含麻风分枝杆菌最具抗原性的成分）的抗原性。对血清反应性蛋白进行N端测序，并使用单核细胞衍生的树突状细胞（DCs）对膜组分进行功能评估，确定主要膜蛋白II（MMP-II）是有效的T细胞激活候选物之一。纯化的MMP-II刺激健康个体的DCs产生白细胞介素-12 p70，并上调主要组织相容性复合体I类和II类、CD86和CD83分子的表面表达。此外，DC群体中CD83(+)细胞的百分比增加。此外，MMP-II脉冲DCs在其表面表达其衍生物。使用依赖Toll样受体2（TLR-2）的受体构建体，我们发现TLR-2信号传导参与了MMP-II诱导的DC成熟。综上所述，就激活抗原呈递细胞和先天免疫而言，MMP-II可被视为一种免疫调节蛋白。
