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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection
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A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection

机译：B淋巴细胞有丝分裂原是持续感染所需的布鲁氏流产毒力因子

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摘要

Microbial pathogens with the ability to establish chronic infections have evolved strategies to actively modulate the host immune response. Brucellosis is a disease caused by a Gram-negative intracellular pathogen that if not treated during the initial phase of the infection becomes chronic as the bacteria persist for the lifespan of the host. How this pathogen and others achieve this action is a largely unanswered question. We report here the identification of a Brucella abortus gene (prpA) directly involved in the immune modulation of the host. PrpA belongs to the proline-racemase family and elicits a B lymphocyte polyclonal activation that depends on the integrity of its proline-racemase catalytic site. Stimulation of splenocytes with PrpA also results in IL-10 secretion. Construction of a B. abortus-prpA mutant allowed us to assess the contribution of PrpA to the infection process. Mice infected with B. abortus induced an early and transient nonresponsive status of splenocytes to both Escherichia coli LIPS and ConA. This phenomenon was not observed when mice were infected with a B. abortus-prpA mutant. Moreover, the B. abortus-prpA mutant had a reduced capacity to establish a chronic infection in mice. We propose that an early and transient nonresponsive immune condition of the host mediated by this B cell polyclonal activator is required for establishing a successful chronic infection by Brucella.
机译：具有建立慢性感染能力的微生物病原体已经进化出可以主动调节宿主免疫反应的策略。布鲁氏菌病是一种由革兰氏阴性细胞内病原体引起的疾病，如果在细菌感染的初始阶段不进行治疗，则该病会随着细菌在宿主的整个生命周期中持续存在而变得慢性。这种病原体和其他病原体如何实现这一作用，在很大程度上尚无答案。我们在这里报告直接参与宿主的免疫调节布鲁氏流产基因（prpA）的鉴定。 PrpA属于脯氨酸外消旋酶家族，其B淋巴细胞多克隆激活取决于其脯氨酸外消旋酶催化位点的完整性。用PrpA刺激脾细胞也会导致IL-10分泌。流产芽孢杆菌-prpA突变体的构建使我们能够评估PrpA对感染过程的贡献。流产双歧杆菌感染的小鼠诱导脾细胞对大肠杆菌LIPS和ConA的早期和短暂的无反应状态。当小鼠感染了流产芽孢杆菌-prpA突变体时，未观察到此现象。而且，流产芽孢杆菌-prpA突变体在小鼠中建立慢性感染的能力降低。我们建议由此B细胞多克隆激活剂介导的宿主的早期和暂时性无反应性免疫状况是建立成功的布鲁氏菌慢性感染所必需的。

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