Use of mouse models to study the variability in virulence associated with specific genotypic lineages of Mycobacterium tuberculosis

Use of mouse models to study the variability in virulence associated with specific genotypic lineages of Mycobacterium tuberculosis
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DOI:
10.1016/j.meegid.2012.02.013
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发表时间:
2012-06-01
影响因子:
3.2
通讯作者:
Mata-Espinosa, D.
Mata-Espinosa, D.
中科院分区:
医学3区
文献类型:
--
作者:
Hernandez-Pando, R.;Marquina-Castillo, B.;Mata-Espinosa, D.

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结核分枝杆菌的宿主反应在那些未能控制感染的患者中表现出广泛的临床表现。感染过程及其流行病学后果取决于宿主、环境和细菌因素的复杂相互作用。实验动物模型有助于确定细菌遗传多样性对毒力和诱导的免疫反应的影响。为此,用从暴发或临床流行病学环境中获得的选定临床分离株感染实验动物,如小鼠、豚鼠和兔。在这里,我们回顾了小鼠模型的贡献,以确定有关分枝杆菌遗传多样性的毒力和免疫反应的变异性。在C57 B1小鼠中的低剂量气溶胶感染或在BALB/c小鼠中的高剂量肠道内感染已经证明了由不同细菌基因型诱导的毒力和免疫应答的广泛变异性,并且每种基因型具有不同的表型,具有高毒力和低毒力变体。总体而言,这些研究表明,来自大集群的高流行菌株比低流行的散发性临床分离株毒力更强,并且高毒力菌株诱导的非保护性免疫应答与临床流行病学数据有一定的相关性。将来,从这些类型的研究中选择的菌株应该用分子技术进行分析。这些研究将有助于鉴定与分枝杆菌毒力和免疫原性相关的基因。(C)2012爱思唯尔有限公司版权所有。
The host response against Mycobacterium tuberculosis show a wide spectrum of clinical manifestations in those patients who fail to control the infection. The course of the infection and its epidemiological consequences depend upon a complex interplay of host, environmental and bacterial factors. Experimental animal models have helped to define the influence of bacterial genetic diversity on virulence and on the immune response that is induced. For this purpose, experimental animals such as mice, guinea pigs and rabbits have been infected with selected clinical isolates obtained from outbreaks or from clinical epidemiology settings. Here we review the contribution of mouse models to defining the variability in virulence and immune response in relation to mycobacterial genetic diversity. Low dose aerosol infection in C57Bl mice or high dose intratracheal infection in BALB/c mice have demonstrated wide variability in virulence and immune responses induced by different bacterial genotypes, and each genotype has different phenotypes, with high and low virulence variants. In general, these studies have shown that high prevalent strains from big clusters are more virulent than low prevalent sporadic clinical isolates, and highly virulent strains induce non-protective immune responses with some correlation with clinical-epidemiological data. In the future selected strains from these types of studies should be analyzed with molecular technologies. These kinds of study will contribute to the identification of mycobacterial genes associated with virulence and immunogenicity. (C) 2012 Elsevier B.V. All rights reserved.