Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host
Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host
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DOI：
10.1073/pnas.0707453104
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发表时间：
2007-09-25
影响因子：
11.1
通讯作者：
Klein, Sabra L.
中科院分区：
文献类型：
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作者：
Easterbrook, Judith D.;Zink, M. Christine;Klein, Sabra L.
汉坦病毒是人畜共患病原体，在其储存宿主中保持持续感染，但介导持续感染的机制仍不清楚。调节性T细胞反应通过抑制促炎性和效应性T细胞活性引起持续性感染;汉坦病毒可能利用这些反应引起持续性感染。为了验证这一假设，雄性挪威大鼠接种首尔病毒和调节性T细胞在感染过程中进行监测。在持续首尔病毒感染期间，雄性大鼠肺中观察到CD 4（+）CD 25（+）叉头盒P3（+）T细胞数量增加以及叉头盒P3和TGF-β表达增加。为了确定调节性T细胞是否调节首尔病毒的持久性，通过使用抗大鼠CD 25单克隆抗体（NDS-63）灭活雄性大鼠中的调节性T细胞。调节性T细胞的失活减少了肺中存在的首尔病毒RNA的数量和唾液中脱落病毒RNA的动物比例。由于调节性T细胞抑制促炎诱导的发病机制，因此在感染期间评估了肺部的病理学观察结果。在感染过程中，在肺中观察到亚临床急性多灶性出血和水肿区域;调节性T细胞的失活减少了病理灶的数量。TNF的表达在感染的持续阶段被抑制;调节性T细胞的失活消除了TNF的抑制。总之，这些数据表明，调节性T细胞介导首尔病毒的持久性，可能是通过提高TGF-β的转录和合成以及抑制TNF。这些数据提供了证据，调节性T细胞参与持久的人畜共患病病原体在其天然水库主机。
Hantaviruses are zoonotic pathogens that maintain a persistent infection in their reservoir hosts, yet the mechanisms mediating persistence remain unknown. Regulatory T cell responses cause persistent infection by suppressing proinflammatory and effector T cell activity; hantaviruses may exploit these responses to cause persistence. To test this hypothesis, male Norway rats were inoculated with Seoul virus and regulatory T cells were monitored during infection. Increased numbers of CD4(+)CD25(+)Forkhead box P3(+) T cells and expression of Forkhead box P3 and TGF-beta were observed in the lungs of male rats during persistent Seoul virus infection. To determine whether regulatory T cells modulate Seoul virus persistence, regulatory T cells were inactivated in male rats by using an anti-rat CD25 monoclonal antibody (NDS-63). Inactivation of regulatory T cells reduced the amount of Seoul virus RNA present in the lungs and the proportion of animals shedding viral RNA in saliva. Because regulatory T cells suppress proinflammatory-induced pathogenesis, pathologic observations in the lungs were evaluated during infection. Subdinical acute multifocal areas of hemorrhage and edema were noted in the lungs during infection; inactivation of regulatory T cells reduced the amount of pathologic foci. Expression of TNF was suppressed during the persistent phase of infection; inactivation of regulatory T cells eliminated the suppression of TNF. Taken together, these data suggest that regulatory T cells mediate Seoul virus persistence, possibly through elevated transcription and synthesis of TGF-beta and suppression of TNF. These data provide evidence of regulatory T cell involvement in the persistence of a zoonotic pathogen in its natural reservoir host.