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

机译:细菌清除可逆转由沙门氏菌感染引起的偏斜的T细胞库

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AbstractSalmonella 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.
机译: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被发现,导致胸腺体积减小,胸腺细胞总数减少。已经表征了双阳性细胞亚群的特异性缺失,但是成熟T细胞向外周的输出仍然是正常的。我们分析了有关胸腺结构和T细胞成熟过程的沙门氏菌发病机理。我们证明,尽管胸腺结构发生了变化,但沙门氏菌感染期间仍维持了T细胞发育,从而允许选择表达特定T细胞受体β链(TCR-Vβ)的单阳性T细胞克隆。此外,用抗生素治疗感染的小鼠恢复了正常的胸腺结构和胸腺细胞亚群分布。另外,治疗后TCR-Vβ的使用频率与未感染小鼠相当。但是,治疗1个月后,仍可从胸腺中回收细菌。我们的数据表明,沙门氏菌感染的胸腺中存在偏斜的T细胞发育过程,从而改变了TCR-Vβ的使用频率。同样,沙门氏菌的治疗后持久性揭示了胸腺作为这种传染原的潜在贮藏库的新功能。

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