The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure.
The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure.
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白介素（IL）-10在愈合后皮肤中持续的持久性以及抗IL-10受体抗体对无菌治疗的治疗潜力的作用。
DOI：
10.1084/jem.194.10.1497
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发表时间：
2001-11-19
期刊：
影响因子：
--
通讯作者：
Sacks DL
中科院分区：
文献类型：
--
作者：
Belkaid Y;Hoffmann KF;Mendez S;Kamhawi S;Udey MC;Wynn TA;Sacks DL
一些病原体(如结核分枝杆菌、弓形虫、利什曼原虫)已被证明在临床治愈后仍在宿主体内，从而确定了疾病复发的风险。我们分析了遗传抗性C57BL/6小鼠皮肤病变自然愈合后长期维持大体利什曼原虫所需的条件。在IL-10缺陷和IL-4/IL-10双缺陷小鼠的无菌治愈中，发现IL-10在寄生虫持续存在中起重要作用。在被感染的沙蝇叮咬的IL-10缺陷小鼠中，证实了在建立与自然感染相关的潜伏期时需要IL-10。宿主-寄生虫的平衡是由CD_4~+和CD_8~+T细胞维持的，它们各自能够释放IL-10或干扰素-γ，并被发现聚集在慢性感染部位，包括皮肤和引流淋巴结。真皮CD_4~+T细胞分泌IL-10和干扰素-γ的频率较高。在慢性期用抗IL-10受体抗体短暂治疗的野生型小鼠实现了无菌治愈，这表明了一种新的治疗方法，可以消除潜伏期、感染库和重新激活疾病的风险。
Some pathogens (e.g., Mycobacterium tuberculosis, Toxoplasma gondii, Leishmania spp) have been shown to persist in their host after clinical cure, establishing the risk of disease reactivation. We analyzed the conditions necessary for the long term maintenance of Leishmania major in genetically resistant C57BL/6 mice after spontaneous healing of their dermal lesions. Interleukin (IL)-10 was found to play an essential role in parasite persistence as sterile cure was achieved in IL-10–deficient and IL-4/IL-10 double-deficient mice. The requirement for IL-10 in establishing latency associated with natural infection was confirmed in IL-10–deficient mice challenged by bite of infected sand flies. The host-parasite equilibrium was maintained by CD4+ and CD8+ T cells which were each able to release IL-10 or interferon (IFN)-γ, and were found to accumulate in chronic sites of infection, including the skin and draining lymph node. A high frequency of the dermal CD4+ T cells released both IL-10 and IFN-γ. Wild-type mice treated transiently during the chronic phase with anti–IL-10 receptor antibodies achieved sterile cure, suggesting a novel therapeutic approach to eliminate latency, infection reservoirs, and the risk of reactivation disease.
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DOI：
10.1084/jem.188.10.1941
发表时间：
1998-11-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Belkaid Y;Kamhawi S;Modi G;Valenzuela J;Noben-Trauth N;Rowton E;Ribeiro J;Sacks DL
通讯作者：
Sacks DL
影响因子：
15.3
作者：
Gerosa, F;Paganin, C;Peritt, D;Paiola, F;Scupoli, MT;AsteAmezaga, M;Frank, I;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
8.6
作者：
Gerosa, F;Nisii, C;Trinchieri, G
通讯作者：
Trinchieri, G
DOI：
10.1084/jem.191.12.2121
发表时间：
2000-06-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bogdan C;Donhauser N;Döring R;Röllinghoff M;Diefenbach A;Rittig MG
通讯作者：
Rittig MG
影响因子：
2.2
作者：
LEZAMADAVILA, CM;WILLIAMS, DM;ALEXANDER, J
通讯作者：
ALEXANDER, J