The thymus is a common target organ in infectious diseases.
The thymus is a common target organ in infectious diseases.
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DOI：
10.1371/journal.ppat.0020062
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发表时间：
2006-06
期刊：
影响因子：
6.7
通讯作者：
Savino W
中科院分区：
文献类型：
--
作者：
Savino W
传染病免疫学主要集中在效应免疫应答、受感染个体的血液和外周淋巴器官的变化以及疫苗开发。对受感染个体胸腺的研究一直被忽视，尽管这种情况正在逐步改变。胸腺是一个初级淋巴器官，能够产生成熟的T细胞，最终定殖次级淋巴器官，因此是必不可少的外周T细胞更新。最近的数据表明，正常的胸腺细胞发育和输出可以改变作为一个感染性疾病的结果。一个共同的特征是感染器官的严重萎缩，主要是由于未成熟的CD4+CD8+胸腺细胞的凋亡相关的耗竭。此外，胸腺细胞增殖经常减少。胸腺的微环境区室也受到影响，特别是在急性感染性疾病中，上皮网络致密化和细胞外基质沉积增加。在查加斯病的鼠模型中，胸腺内趋化因子的产生也增强，并且来自克氏锥虫感染的小鼠的胸腺细胞表现出更多数量的趋化因子和细胞外基质的细胞迁移相关受体，以及对相应配体的迁移反应增加。这种情况与感染动物外周器官中潜在自身反应性胸腺衍生的未成熟CD4+CD8+ T细胞的出现相关。各种传染性病原体包括病毒、原生动物和真菌侵入胸腺，提出了至少对某些传染性病原体衍生抗原产生中枢免疫耐受的假设。很明显，胸腺在各种感染中都是靶向的，这种靶向可能对外周T淋巴细胞的行为产生影响。在这种情况下，胸腺为中心的免疫治疗方法可能代表了一种新的工具，用于治疗严重的传染病。
Infectious disease immunology has largely focused on the effector immune response, changes in the blood and peripheral lymphoid organs of infected individuals, and vaccine development. Studies of the thymus in infected individuals have been neglected, although this is progressively changing. The thymus is a primary lymphoid organ, able to generate mature T cells that eventually colonize secondary lymphoid organs, and is therefore essential for peripheral T cell renewal. Recent data show that normal thymocyte development and export can be altered as a result of an infectious disease. One common feature is the severe atrophy of the infected organ, mainly due to the apoptosis-related depletion of immature CD4+CD8+ thymocytes. Additionally, thymocyte proliferation is frequently diminished. The microenvironmental compartment of the thymus is also affected, particularly in acute infectious diseases, with a densification of the epithelial network and an increase in the deposition of extracellular matrix. In the murine model of Chagas disease, intrathymic chemokine production is also enhanced, and thymocytes from Trypanosoma cruzi-infected mice exhibit greater numbers of cell migration-related receptors for chemokines and extracellular matrix, as well as increased migratory responses to the corresponding ligands. This profile is correlated with the appearance of potentially autoreactive thymus-derived immature CD4+CD8+ T cells in peripheral organs of infected animals. A variety of infectious agents—including viruses, protozoa, and fungi—invade the thymus, raising the hypothesis of the generation of central immunological tolerance for at least some of the infectious agent-derived antigens. It seems clear that the thymus is targeted in a variety of infections, and that such targeting may have consequences on the behavior of peripheral T lymphocytes. In this context, thymus-centered immunotherapeutic approaches potentially represent a new tool for the treatment of severe infectious diseases.
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影响因子：
3.3
作者：
Corrêa-De-Santana, E;Paez-Pereda, M;Savino, W
通讯作者：
Savino, W
DOI：
10.1089/aid.1.1986.2.109
发表时间：
1986-03-01
期刊：
AIDS RESEARCH
影响因子：
--
作者：
INCEFY, GS;PAHWA, S;FIKRIG, S
通讯作者：
FIKRIG, S
影响因子：
4.4
作者：
Fridkis-Hareli, M;Reche, PA;Reinherz, EL
通讯作者：
Reinherz, EL
影响因子：
2.1
作者：
Henriques-Pons, A;DeMeis, J;Araújo-Jorge, TC
通讯作者：
Araújo-Jorge, TC
影响因子：
20.3
作者：
Dalmau, SR;Freitas, CS;Savino, W
通讯作者：
Savino, W