THE CELL BIOLOGY OF LISTERIA-MONOCYTOGENES INFECTION (ESCAPE FROM A VACUOLE)
THE CELL BIOLOGY OF LISTERIA-MONOCYTOGENES INFECTION (ESCAPE FROM A VACUOLE)
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DOI：
10.1111/j.1749-6632.1994.tb44235.x
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发表时间：
1994-01-01
期刊：
影响因子：
--
通讯作者：
JONES, S
中科院分区：
文献类型：
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作者：
PORTNOY, DA;JONES, S
细胞内病原体在全世界造成了极大的发病率和死亡率。令人惊讶的是，我们对细胞内寄生的分子和细胞基础的了解仍处于初级阶段。这样的认识无疑将导致有效的预防和治疗措施。这一领域缺乏进展的部分原因是，在培养许多病原体方面存在困难，而且缺乏有用的遗传系统。这为使用单核细胞增多性李斯特氏菌作为细胞内病原体模型提供了很大的理论基础，可以同时进行遗传和生化分析。此外，单核细胞增多性李斯特氏菌是一个重要的公共卫生问题和严重威胁孕妇、其后代和免疫功能低下个体的病原体。在某些情况下，液泡内的病原体被证明可以防止液泡的酸化和/或液泡与溶酶体的融合。然而，人们对这些过程的细胞生物学、液泡基因表达的调控以及营养获取的具体机制知之甚少。第二类细胞内病原体包括单核细胞增多性李斯特氏菌，由从液泡边界逃逸的寄生虫组成，直接在宿主细胞的细胞质内生长。这两组细胞内病原体的一个共同特征是必须有效地处理寄主液泡的潜在有害环境。有趣的是，至少有四种不同的胞浆内病原体采用的策略是产生与逃离液泡有关的溶血活性。这包括福氏志贺氏菌的接触性溶血素，普氏立克次体的S磷脂酶A2，6和克氏锥虫和单核细胞增多性李斯特菌的成孔溶血素。单核细胞增多性李斯特菌溶血素0(LLO)是本章的重点。单核细胞增多性李氏杆菌是一种重要且危险的人类病原体，也是研究宿主-寄生虫相互作用许多方面的一个很好的模式系统。事实上，单核细胞增多性乳杆菌几十年来一直被免疫学家用作研究小鼠细胞免疫的模型病原体？虽然曾经认为对单核细胞增多性李斯特氏菌的免疫完全可以通过产生激活的巨噬细胞来解释，但现在很明显，对单核细胞增多性李斯特氏菌的免疫反应是多因素的，包括先天免疫反应和获得性反应。在缺乏获得性免疫反应的情况下，如在SCID小鼠中，
Intracellular pathogens are responsible for a devastating amount of morbidity and mortality worldwide. Surprisingly, our understanding of the molecular and cellular basis of intracellular parasitism is still in its infancy. Such an understanding will undoubtedly lead to effective measures for prevention and treatment. The lack of progress in this area is due, in part, to the difficulty in cultivating many of these pathogens and to the lack of useful genetic systems. This provides much of the rationale for the use of Listeria monocytogenes as a model intracellular pathogen amenable to both genetic and biochemical analysis. In addition, L. monocytogenes is a significant public health problem and a serious pathogen which threatens pregnant women, their offspring, and immunocompromised individuals.', 2 Intracellular pathogens can be classified into one of two broad group^.^,^ One group is comprised of organisms that are enclosed by a host vacuolar membrane. Intravacuolar pathogens have been shown in some cases to prevent acidification of the vacuole andor fusion of the vacuole with lysosomes. However, little is known about the cell biology of these processes, the regulation of vacuolar gene expression, and the specific mechanisms of nutrient acquisition. The second group of intracellular pathogens, which includes L. monocytogenes, consists of parasites that escape from the vacuolar confines and grow directly within the cytoplasm of the host cell. A common feature in both groups of intracellular pathogens is the necessity of dealing effectively with the potentially hostile environment of the host vacuole. Interestingly, a strategy adopted by at least four different intracytoplasmic pathogens is the production of hemolytic activity associated with escape from the vacuole. This includes a contact hemolysin for Shigella flexneri, s phospholipase A2 in Rickettsia prowazekii, 6 and a pore-forming hemolysin for Trypanosoma cruzi'and for L. monocytogenes.'The L. monocytogenes hemolysin, listeriolysin 0 (LLO), is the major focus of this chapter.Whereas L. monocytogenes is an important and dangerous human pathogen, it is also a great model system to study many aspects of host-parasite interactions. Indeed, L. monocytogenes has been used by immunologists for decades as a model pathogen in the study of cell-mediated immunity in mice? Although it was once thought that immunity to L. monocytogenes could be entirely explained by the generation of activated macrophages, it is now clear that the immune response to L. monocytogenes is multifactorial, encompassing both an innate immune response" and an acquired response. In the absence of an acquired immune response, as in SCID mice, the