Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses.
Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses.
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DOI：
10.1371/journal.pntd.0008675
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发表时间：
2020-10
影响因子：
3.8
通讯作者：
Soong L
中科院分区：
文献类型：
--
作者：
Fisher J;Card G;Soong L
恙虫病和斑点热立克次体病是未得到充分研究的具有全球意义的病媒传播疾病。在横跨东亚和南亚到北方澳大利亚的地方性地区，仅丛林斑疹伤寒就有超过10亿人面临风险。虽然高度可治疗，但诊断挑战使得这些疾病难以及时进行抗生素干预。延迟治疗可能导致影响多个器官的严重结局，包括中枢神经系统（CNS），其中感染和相关的神经炎症可能是致命的或导致持久的后遗症。脑膜炎和脑炎在恙虫病和SFR中都很流行。此外，详细描述局灶性神经功能缺损的病例报告已经曝光，并关注感染的急性和慢性后遗症。尽管越来越多的临床报告概述了这些疾病的神经系统后果，但相对较少的研究探讨了神经炎症的潜在机制。恙虫病的动物模型已经确定了与内皮感染和神经发病机制相关的脑T细胞浸润和血管损伤。鼠恙虫病期间脑组织的差异基因表达分析揭示了CXCR3配体、促炎和1型细胞因子和趋化因子、细胞毒性分子的选择性增加，以及补体途径的改变。在SFR中，小胶质细胞扩张和巨噬细胞浸润有助于神经系统疾病进展。这篇叙述性综述强调了恙虫病和SFR的临床神经学特征，并评估了我们目前对这两种疾病动物模型神经炎症基础研究的理解。进一步研究神经发病机制的关键介质可能会产生严重患者的预后指标和治疗方案。
Scrub typhus and spotted fever rickettsioses (SFR) are understudied, vector-borne diseases of global significance. Over 1 billion individuals are at risk for scrub typhus alone in an endemic region, spanning across eastern and southern Asia to Northern Australia. While highly treatable, diagnostic challenges make timely antibiotic intervention difficult for these diseases. Delayed therapy may lead to severe outcomes affecting multiple organs, including the central nervous system (CNS), where infection and associated neuroinflammation may be lethal or lead to lasting sequelae. Meningitis and encephalitis are prevalent in both scrub typhus and SFR. Additionally, case reports detailing focal neurological deficits have come to light, with attention to both acute and chronic sequelae of infection. Despite the increasing number of clinical reports outlining neurologic consequences of these diseases, relatively little research has examined underlying mechanisms of neuroinflammation. Animal models of scrub typhus have identified cerebral T-cell infiltration and vascular damage associated with endothelial infection and neuropathogenesis. Differential gene expression analysis of brain tissues during murine scrub typhus have revealed selective increases in CXCR3 ligands, proinflammatory and type-1 cytokines and chemokines, and cytotoxicity molecules, as well as alterations in the complement pathway. In SFR, microglial expansion and macrophage infiltration contribute to neurological disease progression. This narrative Review highlights clinical neurologic features of scrub typhus and SFR and evaluates our current understanding of basic research into neuroinflammation for both diseases in animal models. Further investigation into key mediators of neuropathogenesis may yield prognostic markers and treatment regimens for severe patients.
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影响因子：
11.8
作者：
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通讯作者：
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3.8
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