Understanding tropism and immunopathological mechanisms of relapsing fever spirochaetes.
Understanding tropism and immunopathological mechanisms of relapsing fever spirochaetes.
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DOI：
10.1111/j.1469-0691.2009.02785.x
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Londoño D
中科院分区：
文献类型：
--
作者：
Cadavid D;Londoño D
感染回归热（RF）螺旋体的小鼠在反复出现的高水平菌血症中存活下来，几乎没有临床并发症或组织损伤。在缺乏 B 细胞的情况下，菌血症峰值不会消失，从而导致多器官并发症。在菌血症高峰期，血液和组织中会产生大量白介素 10 (IL-10)。在无法清除菌血症峰值的小鼠中，外源性 IL-10 大大降低了临床表现、CXCL13 血清水平、脑小胶质细胞增生和病原体负荷。相比之下，缺乏IL-10的小鼠无法清除菌血症峰值，导致微血管并发症的严重程度不同，具体取决于血清型：血清型2 (Bt2)，它会导致c. 菌血症峰值。 108/mL，导致蛛网膜下腔和实质内出血迅速死亡；相反，血清型 1 会导致 c 菌血症峰值。 107/mL，导致较轻的多器官出血和血栓形成。尽管菌血症峰值较低，但 IL-10 缺乏也会导致野生型小鼠多器官出血和血栓形成并伴有梗塞。已经确定了两种病原体控制机制：峰值菌血症的抗体清除，以及通过脾脏中的吞噬作用独立于抗体降低菌血症。根据菌血症的严重程度，IL-10 在病原体控制中发挥相反的作用：在持续高菌血症期间，IL-10 通过保护先天免疫细胞免于凋亡来帮助控制菌血症；相反，在短暂的菌血症高峰期间，IL-10 会减慢抗体介导的清除率。 RF 的成功结果取决于平衡的免疫反应，以清除菌血症，同时避免微血管损伤，其中针对病原体负荷产生的 IL-10 发挥着关键作用。
Mice infected with relapsing fever (RF) spirochaetes survive recurrent waves of high-level bacteraemia with little, if any, clinical complications or tissue injury. In the absence of B-cells, peak bacteraemia does not resolve, resulting in multi-organ complications. During peak bacteraemia, large amounts of interleukin-10 (IL-10) are produced in blood and tissues. In mice unable to clear peak bacteraemia, exogenous IL-10 greatly reduced the clinical manifestations, serum levels of CXCL13, cerebral microgliosis, and the pathogen load. In contrast, IL-10 deficiency in mice unable to clear peak bacteraemia resulted in microvascular complications with distinct severities, depending on the serotype: serotype 2 (Bt2), which causes peak bacteraemia of c. 108/mL, resulted in rapid death from subarachnoid and intraparenchymal haemorrhage; in contrast, serotype 1, which causes peak bacteraemia of c. 107/mL, resulted in milder multi-organ haemorrhage and thrombosis. IL-10 deficiency also resulted in multi-organ haemorrhage and thrombosis with infarction in wild-type mice despite lower peak bacteraemia. Two mechanisms for pathogen control have been identified: antibody clearance of peak bacteraemia, and antibody-independent lowering of bacteraemia via phagocytosis in the spleen. IL-10 plays opposite roles in pathogen control, depending on the severity of bacteraemia: during persistent high bacteraemia, IL-10 helps to control it by protecting innate immune cells from apoptosis; in contrast, during transient peak bacteraemia, IL-10 slows down antibody-mediated clearance. A successful outcome from RF depends on a balanced immune response to clear bacteraemia while avoiding microvascular injury, in which production of IL-10, in response to the pathogen load, plays a critical role.
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影响因子：
3.1
作者：
Brown, JP;Zachary, JF;Wooten, RM
通讯作者：
Wooten, RM
DOI：
10.1073/pnas.0605302103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Barbour, Alan G.;Dai, Qiyuan;Frank, Steven A.
通讯作者：
Frank, Steven A.
影响因子：
20.3
作者：
Alugupalli, KR;Michelson, AD;Leong, JM
通讯作者：
Leong, JM
影响因子：
6.4
作者：
Cadavid, D;Sondey, M;Lawson, CL
通讯作者：
Lawson, CL
影响因子：
3.1
作者：
Londoño, D;Bai, YH;Cadavid, D
通讯作者：
Cadavid, D