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细菌清除可逆转沙门氏菌感染诱导的 T 细胞受体偏倚。

Bacterial clearance reverses a skewed T-cell repertoire induced by Salmonella infection.

机构信息

Doctorado en Ciencias Biomédicas Facultad de Medicina, UNAM Mexico City, CP 045510, Mexico ; Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV) Mexico City.

Hospital General la Raza, Instituto Mexicano del Seguro Social (IMSS) Mexico City.

出版信息

Immun Inflamm Dis. 2015 Sep;3(3):209-23. doi: 10.1002/iid3.60. Epub 2015 May 6.

Abstract

Salmonella typhimurium invades the spleen, liver, and peripheral lymph nodes and has recently been detected in the bone marrow and thymus, resulting in a reduced thymic size and a decline in the total number of thymic cells. A specific deletion of the double-positive cell subset has been characterized, yet the export of mature T cells to the periphery remains normal. We analyzed Salmonella pathogenesis regarding thymic structure and the T-cell maturation process. We demonstrate that, despite alterations in the thymic structure, T-cell development is maintained during Salmonella infection, allowing the selection of single-positive T-cell clones expressing particular T-cell receptor beta chains (TCR-Vβ). Moreover, the treatment of infected mice with an antibiotic restored the normal thymic architecture and thymocyte subset distribution. Additionally, the frequency of TCR-Vβ usage after treatment was comparable to that in non-infected mice. However, bacteria were still recovered from the thymus after 1 month of treatment. Our data reveal that a skewed T-cell developmental process is present in the Salmonella-infected thymus that alters the TCR-Vβ usage frequency. Likewise, the post-treatment persistence of Salmonella reveals a novel function of the thymus as a potential reservoir for this infectious agent.

摘要

鼠伤寒沙门氏菌侵袭脾脏、肝脏和外周淋巴结,最近在骨髓和胸腺中也有发现,导致胸腺体积缩小,胸腺细胞总数减少。已经对双阳性细胞亚群的特异性缺失进行了特征描述,但成熟 T 细胞向外周的输出仍然正常。我们分析了沙门氏菌发病机制与胸腺结构和 T 细胞成熟过程的关系。我们证明,尽管胸腺结构发生改变,但在沙门氏菌感染期间 T 细胞发育仍能维持,允许表达特定 T 细胞受体β链(TCR-Vβ)的单阳性 T 细胞克隆的选择。此外,用抗生素治疗感染小鼠可恢复正常的胸腺结构和胸腺细胞亚群分布。此外,治疗后 TCR-Vβ的使用频率与未感染小鼠相当。然而,即使经过 1 个月的治疗,仍能从胸腺中回收细菌。我们的数据揭示了沙门氏菌感染的胸腺中存在偏向的 T 细胞发育过程,改变了 TCR-Vβ的使用频率。同样,治疗后沙门氏菌的持续存在揭示了胸腺的一个新功能,即作为这种感染因子的潜在储库。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dc2/4578521/39d36c625252/iid30003-0209-f1.jpg

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