Wargnier A, Sasportes M, Lagrange P H
Service de microbiologie, université Paris 7, hôpital Saint-Louis, 1 avenue Claude-Vellefaux, 75010 Paris, France.
Pathol Biol (Paris). 2005 Oct-Nov;53(8-9):516-21. doi: 10.1016/j.patbio.2005.07.003. Epub 2005 Aug 2.
The recent global increase in cases of tuberculosis and the emergence of multidrug-resistant strains of tuberculosis have focused attention on the molecular mechanisms of human antimycobacterial immunity. The macrophage is not only the primary site for Mycobacterium tuberculosis growth but also ordinarily provides the primary lines of host defense against invading pathogens in its role as an effector of innate immunity. The ability of M. tuberculosis to survive and replicate in the host macrophage is critical to its pathogenesis, emphasizing a need for a clearer understanding of its interactions with the host macrophage. Macrophages use varied strategies to kill and destroy invading organisms, including production of reactive nitrogen and oxygen intermediates, phagosome maturation and acidification, fusion with lysosomes, exposure to defensins and host cell apoptosis. In human, granulysin is a recently identified antimicrobial protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown that granulysin contributes to the defense mechanisms against mycobacterial infection. We hypothesized that human macrophages may possess antimicrobial substances, such as granulysin, and play a role in the defense mechanism.
近期全球结核病病例增加以及多重耐药结核菌株的出现,使得人们将注意力集中在人类抗分枝杆菌免疫的分子机制上。巨噬细胞不仅是结核分枝杆菌生长的主要场所,而且作为固有免疫的效应器,通常还提供宿主抵御入侵病原体的主要防线。结核分枝杆菌在宿主巨噬细胞内存活和复制的能力对其发病机制至关重要,这强调了更清楚地了解其与宿主巨噬细胞相互作用的必要性。巨噬细胞采用多种策略来杀死和破坏入侵的生物体,包括产生活性氮和氧中间体、吞噬体成熟和酸化、与溶酶体融合、接触防御素以及宿主细胞凋亡。在人类中,颗粒溶素是一种最近在细胞毒性T细胞、自然杀伤(NK)细胞和NKT细胞上发现的抗菌蛋白。研究表明,颗粒溶素有助于抵御分枝杆菌感染的防御机制。我们推测人类巨噬细胞可能拥有诸如颗粒溶素之类的抗菌物质,并在防御机制中发挥作用。