IL-10 Dampens TNF/Inducible Nitric Oxide Synthase-Producing Dendritic Cell-Mediated Pathogenicity during Parasitic Infection
IL-10 Dampens TNF/Inducible Nitric Oxide Synthase-Producing Dendritic Cell-Mediated Pathogenicity during Parasitic Infection
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DOI：
10.4049/jimmunol.182.2.1107
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发表时间：
2009-01-15
影响因子：
4.4
通讯作者：
Beschin, Alain
中科院分区：
文献类型：
--
作者：
Guilliams, Martin;Movahedi, Kiavash;Beschin, Alain
抗寄生虫反应与单核细胞的募集有关，单核细胞在感染部位分化为巨噬细胞和树突细胞。尽管经典激活的单核细胞被认为是布氏锥虫感染期间 TNF 和 NO 的主要来源，但其细胞起源仍不清楚。在这项研究中，我们发现骨髓源性单核细胞在布氏锥虫感染小鼠的脾脏、肝脏和淋巴结中积累并分化为产生 TNF/诱导型 NO 合酶的树突状细胞 (TIP-DC)。尽管 TIP-DC 已被证明在消除几种细胞内病原体方面发挥有益作用，但我们报告说，TIP-DC 作为发炎器官中 TNF 和 NO 的主要来源，可能在布氏锥虫感染的慢性阶段对组织损伤做出积极贡献。此外，IL-10的缺失导致单核细胞向TIP-DC的分化增强，导致宿主致病性加剧和过早死亡。最后，我们证明，用腺相关病毒载体对慢性感染小鼠进行 IL-10 基因递送治疗后，IL-10 的持续产生限制了单核细胞向 TIP-DC 的分化，并保护宿主免受组织损伤。免疫学杂志，2009，182：1107-1118。
Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at the site of infection. Although classically activated monocytic cells are assumed to be the major source of TNF and NO during Trypanosoma brucei brucei infection, their cellular origin remains unclear. In this study, we show that bone marrow-derived monocytes accumulate and differentiate to TNF/inducible NO synthase-producing dendritic cells (TIP-DCs) in the spleen, liver, and lymph nodes of T. brucei brucei-infected mice. Although TIP-DCs have been shown to play a beneficial role in the elimination of several intracellular pathogens, we report that TIP-DCs, as a major source of TNF and NO in inflamed organs, could contribute actively to tissue damage during the chronic stage of T. brucei brucei infection. In addition, the absence of IL-10 leads to enhanced differentiation of monocytes to TIP-DCs, resulting in exacerbated pathogenicity and early death of the host. Finally, we demonstrate that sustained production of IL-10 following IL-10 gene delivery treatment with an adeno-associated viral vector to chronically infected mice limits the differentiation of monocytes to TIP-DCs and protects the host from tissue damage. The Journal of Immunology, 2009,182: 1107-1118.