Plasticity in early immune evasion strategies of a bacterial pathogen
Plasticity in early immune evasion strategies of a bacterial pathogen
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DOI：
10.1073/pnas.1718595115
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发表时间：
2018-04-17
影响因子：
11.1
通讯作者：
Pal, Utpal
中科院分区：
文献类型：
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作者：
Bernard, Quentin;Smith, Alexis A.;Pal, Utpal
伯氏疏螺旋体是为数不多的能够在哺乳动物中建立持续感染的胞外病原体之一。维持这种细菌长期生存的机制在很大程度上是未知的。在这里，我们报告了一种独特的伯氏杆菌天然免疫逃避策略，由一种被注释为BBA57的表面蛋白通过其对多个螺旋体毒力决定因素的调节来协调。BBA57功能对于早期感染是关键的，但对于螺旋体持续的后期阶段来说，无论是在哺乳动物中还是在扁虱中，BBA57功能都是多余的。该蛋白影响宿主干扰素应答，并抑制多种宿主杀菌活性，包括血清补体、中性粒细胞和抗菌肽。我们还发现BBA57介导的螺旋体免疫逃避策略具有显著的可塑性，因为它的丢失虽然导致病原体在接种部位几乎被清除，但会触发非遗传的适应性变化，排除基因组中可检测到的核苷酸变化，但包括转录重编程事件。了解螺旋体免疫逃避机制的延展性，确保其宿主的持久性，对于开发新的治疗和预防方法来对抗莱姆疏螺旋体病等长期感染至关重要。
Borrelia burgdorferi is one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy of B. burgdorferi, orchestrated by a surface protein annotated as BBA57, through its modulation of multiple spirochete virulent determinants. BBA57 function is critical for early infection but largely redundant for later stages of spirochetal persistence, either in mammals or in ticks. The protein influences host IFN responses as well as suppresses multiple host microbicidal activities involving serum complement, neutrophils, and antimicrobial peptides. We also discovered a remarkable plasticity in BBA57-mediated spirochete immune evasion strategy because its loss, although resulting in near clearance of pathogens at the inoculum site, triggers nonheritable adaptive changes that exclude detectable nucleotide alterations in the genome but incorporate transcriptional reprograming events. Understanding the malleability in spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel therapeutic and preventive approaches to combat long-term infections like Lyme borreliosis.