T-cell tolerance and exhaustion in the clearance of Echinococcus multilocularis: role of inoculum size in a quantitative hepatic experimental model.
T-cell tolerance and exhaustion in the clearance of Echinococcus multilocularis: role of inoculum size in a quantitative hepatic experimental model.
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多房棘球绦虫清除过程中的 T 细胞耐受性和耗竭：接种量在定量肝脏实验模型中的作用
DOI：
10.1038/s41598-017-11703-1
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发表时间：
2017-09-11
影响因子：
4.6
通讯作者：
Wen H
中科院分区：
文献类型：
--
作者：
Zhang C;Shao Y;Yang S;Bi X;Li L;Wang H;Yang N;Li Z;Sun C;Li L;Lü G;Aji T;Vuitton DA;Lin R;Wen H
在E的发展过程中，导致自我修复或持续慢性感染的局部免疫机制尚不清楚。多房性幼虫。在这里，我们开发了一个合适的实验模型，根据寄生虫的负载模拟自然感染的肝脏。我们证明，局部细胞免疫和纤维化实际上是保护性的，完全能够限制低或中剂量感染小鼠(LDG或MDG)肝脏中的后生线虫生长，甚至清除它，而在高剂量感染小鼠(HDG)中，细胞免疫受损之后会出现更快和更严重的病程。记忆T细胞(包括CD4Tem、CD8Tem和CD8Tem)的募集和/或增殖以及肝脏中T1/T2/T17/Treg类型T细胞的失衡不仅与LDG中寄生虫感染的清除有关，而且与HDG中肝脏损伤的增加有关，尤其是CD8T细胞的双重作用依赖于寄生虫载量和不同阶段的寄生虫生长。此外，我们首次证明了表达LAG3或2B4的T细胞耗竭与晚期HD接种之间的关系。我们的定量实验模型似乎完全适合研究免疫调节作为泡状棘球绦虫病患者的治疗策略。
The local immune mechanisms responsible for either self-healing or sustained chronic infection are not clear, in the development ofE. multilocularislarvae. Here, we developed a suitable experimental model that mimics naturally infected livers, according to the parasite load. We demonstrated that local cellular immunity and fibrogenesis are actually protective and fully able to limit metacestode growth in the liver of low or medium dose-infected mice (LDG or MDG), or even to clear it, while impairment of cellular immunity is followed by a more rapid and severe course of the disease in high dose-infected mice (HDG). And recruitment and/ or proliferation of memory T cells (including CD4 Tem, CD8 Tcm and CD8 Tem) and imbalance of T1/T2/T17/Treg-type T cells in liver were not only associated with clearance of the parasite infection in LDG, but also with increased hepatic injury in HDG; in particular the dual role of CD8 T cells depending on the parasite load and the various stages of metacestode growth. Besides, we first demonstrate the association between LAG3- or 2B4-expressing T cells exhaustion and HD inocula in late stages. Our quantitative experimental model appears fully appropriate to study immunomodulation as a therapeutic strategy for patients with Alveolar Echinococcosis.
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影响因子：
30.5
作者：
Butler, Noah S.;Moebius, Jacqueline;Pewe, Lecia L.;Traore, Boubacar;Doumbo, Ogobara K.;Tygrett, Lorraine T.;Waldschmidt, Thomas J.;Crompton, Peter D.;Harty, John T.
通讯作者：
Harty, John T.
影响因子：
4.6
作者：
Nguyen HH;Kim T;Song SY;Park S;Cho HH;Jung SH;Ahn JS;Kim HJ;Lee JJ;Kim HO;Cho JH;Yang DH
通讯作者：
Yang DH
影响因子：
11.8
作者：
Chauchet, Adrien;Grenouillet, Frederic;Bresson-Hadni, Solange
通讯作者：
Bresson-Hadni, Solange
影响因子：
4.4
作者：
Gomes-Pereira, S;Rodrigues, OR;Santos-Gomes, GM
通讯作者：
Santos-Gomes, GM
影响因子：
4.6
作者：
LIANCE, M;BRESSONHADNI, S;VUITTON, DA
通讯作者：
VUITTON, DA