Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Posttreatment in Rhesus Macaques.
Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Posttreatment in Rhesus Macaques.
复制标题
DOI：
10.1016/j.ajpath.2017.11.005
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Embers ME
中科院分区：
文献类型：
--
作者：
Crossland NA;Alvarez X;Embers ME
非人灵长类动物目前作为莱姆病的最佳实验模型，因为它们与人类的遗传同源性密切，并证明了感染伯氏疏螺旋体后疾病的所有三个阶段。我们研究了多西环素治疗（28天; 5 mg/kg，口服，每日两次）和未治疗的恒河猴中与晚期播散性莱姆病（蜱接种后12至13个月）相关的病理学。在多个组织中观察到极轻微至中度淋巴浆细胞性炎症，且好发于血管周围间隙和胶原组织，包括脑软脑膜、脑干、前肢和后肢的外周神经、后膝关节滑膜和滑膜周围脂肪组织、膀胱、骨骼肌、心肌和心包脏层。对含有炎症的所有组织切片进行单克隆（外表面蛋白A）和多克隆抗体结合的间接免疫荧光测定。在两只给药恒河猴的大脑、一只给药恒河猴的心脏和一只未给药动物的周围神经附近观察到罕见的形态完整的螺旋体。在给药和未给药动物的心脏、骨骼肌和周围神经附近也观察到可能的螺旋体横截面的疏螺旋体抗原染色。这些发现支持了慢性莱姆病症状可归因于组织内和周围的残留炎症的观点，这些组织具有低负荷的持续宿主适应性螺旋体和/或残留抗原。
Nonhuman primates currently serve as the best experimental model for Lyme disease because of their close genetic homology with humans and demonstration of all three phases of disease after infection with Borrelia burgdorferi. We investigated the pathology associated with late disseminated Lyme disease (12 to 13 months after tick inoculation) in doxycycline-treated (28 days; 5 mg/kg, oral, twice daily) and untreated rhesus macaques. Minimal to moderate lymphoplasmacytic inflammation, with a predilection for perivascular spaces and collagenous tissues, was observed in multiple tissues, including the cerebral leptomeninges, brainstem, peripheral nerves from both fore and hind limbs, stifle synovium and perisynovial adipose tissue, urinary bladder, skeletal muscle, myocardium, and visceral pericardium. Indirect immunofluorescence assays that combined monoclonal (outer surface protein A) and polyclonal antibodies were performed on all tissue sections that contained inflammation. Rare morphologically intact spirochetes were observed in the brains of two treated rhesus macaques, the heart of one treated rhesus macaque, and adjacent to a peripheral nerve of an untreated animal. Borrelia antigen staining of probable spirochete cross sections was also observed in heart, skeletal muscle, and near peripheral nerves of treated and untreated animals. These findings support the notion that chronic Lyme disease symptoms can be attributable to residual inflammation in and around tissues that harbor a low burden of persistent host-adapted spirochetes and/or residual antigen.
登录
查看更多内容
DOI：
10.1093/cid/ciu397
发表时间：
2014-09-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Hinckley AF;Connally NP;Meek JI;Johnson BJ;Kemperman MM;Feldman KA;White JL;Mead PS
通讯作者：
Mead PS
影响因子：
3.7
作者：
Embers, Monica E.;Barthold, Stephen W.;Philipp, Mario T.
通讯作者：
Philipp, Mario T.
影响因子：
5
作者：
Bai, YH;Narayan, K;Cadavid, D
通讯作者：
Cadavid, D
影响因子：
56.9
作者：
Gibbs, Richard A.;Rogers, Jeffrey;Zwieg, Ann S.
通讯作者：
Zwieg, Ann S.
影响因子：
--
作者：
Embers, Monica E.;Hasenkampf, Nicole R.;Tardo, Amanda C.
通讯作者：
Tardo, Amanda C.