Division of Immunology, Tulane National Primate Research Center, Tulane University Health Sciences, Covington, Louisiana, USA
Department of Pediatrics, National School of Tropical Medicine, Houston, Texas, USA.
Infect Immun. 2019 Mar 25;87(4). doi: 10.1128/IAI.00900-18. Print 2019 Apr.
The global public health impact of relapsing fever (RF) spirochetosis is significant, since the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques with (a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody responses to specific antigens, and peripheral lymphocyte population dynamics. Our results indicate that elicits from peripheral blood cells key inflammatory response mediators (interleukin-1β and tumor necrosis factor alpha), which are associated with preterm abortion. Moreover, a global decline in peripheral B-cell populations was observed in all animals at 14 days postinfection. Serological responses were also evaluated to assess the antigenicity of three surface proteins: BipA, BrpA, and Bta112. Interestingly, a distinction was observed between antibodies generated in nonhuman primates and mice. Our results provide support for the nonhuman primate model not only in studies of prenatal pathogenesis but also for diagnostic and vaccine antigen identification and testing.
回归热(RF)螺旋体病在全球范围内对公共卫生的影响重大,因为病原体存在于七大洲中的五个洲。感染的显著标志是间歇性发热,最大的威胁是针对未出生的婴儿。为了更好地了解 B 细胞反应的特异性以及免疫反应在致病性中的作用,我们通过蜱叮咬感染恒河猴(一种新世界 RF 螺旋体物种),并监测针对病原体产生的免疫反应。具体来说,我们评估了病原体引起的炎症介质诱导、宿主对特定抗原的抗体反应以及外周淋巴细胞群体动态。我们的结果表明, 从外周血细胞中引发关键的炎症反应介质(白细胞介素-1β和肿瘤坏死因子-α),这些介质与早产流产有关。此外,在感染后 14 天,所有动物的外周 B 细胞群体均出现全球性下降。我们还评估了血清学反应,以评估三种表面蛋白(BipA、BrpA 和 Bta112)的抗原性。有趣的是,在非人类灵长类动物和小鼠中产生的抗体之间观察到了区别。我们的结果不仅为研究产前发病机制提供了支持,也为诊断和疫苗抗原的鉴定和测试提供了支持,非人类灵长类动物模型不仅如此。