Schlüter D, Domann E, Buck C, Hain T, Hof H, Chakraborty T, Deckert-Schlüter M
Institut für Medizinische Mikrobiologie und Hygiene, Universit atsklinikum Mannheim, Universität Heidelberg, Mannheim, Germany.
Infect Immun. 1998 Dec;66(12):5930-8. doi: 10.1128/IAI.66.12.5930-5938.1998.
Meningoencephalitis is a serious and often fatal complication of Listeria monocytogenes infection. The aim of the present study was to analyze the role of internalin A (InlA) and B, which are involved in the invasion of L. monocytogenes into cultivated host tissue cells, and that of phosphatidylcholine-specific phospholipase C (PlcB), which mainly promotes the direct cell-to-cell spread of L. monocytogenes, in murine cerebral listeriosis by use of an InlA/B (DeltainlAB2)- and a PlcB (DeltaplcB2)-deficient isogenic deletion mutant strain and the wild-type (WT) L. monocytogenes EGD. Listeria strains were directly applied to the brain, a technique which has been employed previously to study the pathogenesis of cerebral listeriosis (D. Schlüter, S. B. Oprisiu, S. Chahoud, D. Weiner, O. D. Wiestler, H. Hof, and M. Deckert-Schlüter, Eur. J. Immunol. 25:2384-2391, 1995). We demonstrated that PlcB, but not InlA or InlB, is an important virulence factor in cerebral listeriosis. Nonimmunized mice infected intracerebrally with the DeltaplcB2 strain survived significantly longer and had a reduced intracerebral bacterial load compared to mice infected with the DeltainlAB2 strain or WT bacteria. In addition, immunization with the WT prior to intracerebral infection significantly increased the survival rate of mice challenged intracerebrally with the DeltaplcB2 strain compared to that of mice infected with the WT or DeltainlAB2 strain. Histopathology revealed that the major difference between the various experimental groups was a significantly delayed intracerebral spread of the DeltaplcB2 mutant strain, indicating that cell-to-cell spread is an important pathogenic feature of cerebral listeriosis. Interestingly, irrespective of the Listeria mutant used, the apoptosis of hippocampal and cerebellar neurons and an internal hydrocephalus developed in surviving mice, indicating that these complications are not dependent on the virulence factors InlA/B and PlcB. In conclusion, this study points to PlcB as a virulence factor important for the intracerebral pathogenesis of murine L. monocytogenes meningoencephalitis.
脑膜炎脑炎是单核细胞增生李斯特菌感染的一种严重且往往致命的并发症。本研究的目的是通过使用InlA/B（DeltainlAB2）和磷脂酰胆碱特异性磷脂酶C（PlcB，DeltaplcB2）缺陷的同基因缺失突变株以及野生型（WT）单核细胞增生李斯特菌EGD，分析参与单核细胞增生李斯特菌侵入培养的宿主组织细胞的内化素A（InlA）和B以及主要促进单核细胞增生李斯特菌细胞间直接传播的磷脂酰胆碱特异性磷脂酶C（PlcB）在小鼠脑李斯特菌病中的作用。将李斯特菌菌株直接接种到大脑，该技术先前已用于研究脑李斯特菌病的发病机制（D. Schlüter、S. B. Oprisiu、S. Chahoud、D. Weiner、O. D. Wiestler、H. Hof和M. Deckert-Schlüter，《欧洲免疫学杂志》25:2384 - 2391，1995年）。我们证明，在脑李斯特菌病中，PlcB是一种重要的毒力因子，而InlA或InlB不是。与感染DeltainlAB2菌株或野生型细菌的小鼠相比，脑内感染DeltaplcB2菌株的未免疫小鼠存活时间显著延长，脑内细菌载量降低。此外，与感染野生型或DeltainlAB2菌株的小鼠相比，脑内感染前用野生型进行免疫显著提高了脑内感染DeltaplcB2菌株的小鼠的存活率。组织病理学显示，各实验组之间的主要差异是DeltaplcB2突变株的脑内传播显著延迟，这表明细胞间传播是脑李斯特菌病的一个重要致病特征。有趣的是，无论使用哪种李斯特菌突变株，存活小鼠的海马和小脑神经元都会发生凋亡并出现内部脑积水，这表明这些并发症不依赖于毒力因子InlA/B和PlcB。总之，本研究指出PlcB是对小鼠单核细胞增生李斯特菌脑膜炎脑炎脑内发病机制重要的毒力因子。
