Alternative versus classical macrophage activation during experimental African trypanosomosis
Alternative versus classical macrophage activation during experimental African trypanosomosis
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DOI：
10.1016/s0020-7519(01)00170-9
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发表时间：
2001-05-01
影响因子：
4
通讯作者：
Beschin, A
中科院分区：
文献类型：
--
作者：
De Baetselier, P;Namangala, B;Beschin, A
非洲锥虫是一种细胞外寄生虫，会导致撒哈拉以南非洲地区的人类昏睡病或牲畜纳加那病。为了深入了解控制这些寄生虫的抗性/易感性的因素，比较了感染布氏锥虫磷脂酶 C 无效突变体 (PLC-/-) 或其野生型对应物 (WT) 的小鼠的免疫反应。我们发现 T. b.诱导慢性感染的布鲁氏菌突变体在感染的早期阶段触发I型细胞因子的产生，随后在疾病的晚期/慢性阶段分泌II型细胞因子。相比之下，WT 感染的小鼠在 5 周内被杀死，并保持 I 型细胞因子反应。 I 型/II 型细胞因子平衡可能会影响抑制性巨噬细胞不同亚群的发育，即经典激活的巨噬细胞（I 型）与拮抗调节的替代激活的巨噬细胞（II 型）。因此，在 WT 和 PLC-/- T 期间引发了巨噬细胞的表型和辅助细胞功能。布氏感染问题得到解决。结果表明，在 WT 和 PLC-/- 锥虫感染的早期阶段，经典激活的巨噬细胞在 I 型细胞因子环境中发育。在感染后期，只有PLC-/-感染的小鼠能够抵抗感染，从而产生II型细胞因子相关的替代巨噬细胞。与此同时，我们发现，对刚果锥虫感染敏感的小鼠，寄生虫呈指数增长直至死亡，在感染早期阶段，其 II 型细胞因子水平高于控制寄生虫血症第一个高峰的抗性动物。刚果锥虫耐药小鼠和敏感小鼠中 I 型细胞因子的水平相当。基于这些结果，我们提出，非洲锥虫感染的存活需要I型细胞因子环境和感染早期经典的巨噬细胞激活，使小鼠能够控制寄生虫血症的第一个高峰。此后，需要切换到 II 型细胞因子环境，触发替代性巨噬细胞激活，以使疾病进展到慢性期。感染晚期/慢性阶段替代巨噬细胞的顺序激活可能在小鼠对 PLC-/- T. b 的抵抗力增加中发挥作用。布鲁切伊将被讨论。 (C) 2001 年澳大利亚寄生虫学协会。由 Elsevier Science Ltd 出版。保留所有权利。
African trypanosomes are extracellular parasites causing sleeping sickness to human or nagana to livestock in sub-Saharan Africa. To gain insight into factors governing resistance/susceptibility to these parasites, the immune responses in mice infected with a Trypanosoma brucei phospholipase C null mutant (PLC-/-) or its wild type counterpart (WT) were compared. We found that the T. b. brucei mutant inducing a chronic infection triggers the production of type I cytokines during the early stage of infection, followed by the secretion of type II cytokines in the late/chronic phase of the disease. In contrast, WT-infected mice are killed within 5 weeks and remain locked in a type I cytokine response. The type I/type II cytokine balance may influence the development of different subsets of suppressive macrophages, i.e. classically activated macrophages (type I) versus alternatively activated macrophages (type II) that are antagonistically regulated. Therefore, the phenotype and accessory cell function of macrophages elicited during WT and PLC-/- T. b. brucei infections were addressed. Results indicate that classically activated macrophages develop in a type I cytokine environment in the early phase of both WT and PLC-/- trypanosome infections. In the late stage of infection, only PLC-/--infected mice resisting the infection develop type II cytokine-associated alternative macrophages. In parallel, we found that mice susceptible to Trypanosoma congolense infection, showing an exponential parasite growth until they die, have a higher lever of type II cytokines in the early stage of infection than resistant animals controlling the first peak of parasitaemia. The levels of type I cytokines were comparable in both T. congolense-resistant and -susceptible mice. On the basis of these results, we propose that survival to African trypanosome infection requires a type I cytokine environment and classical macrophage activation in the early stage of infection, enabling mice to control the first peak of parasitaemia. Thereafter, a switch to type II cytokine environment triggering alternative macrophage activation is required to enable progression of the disease into the chronic phase. The possible role of the sequential activation of alternative macrophages in the late/chronic stage of infection in the increased resistance of mice to PLC-/- T. b. brucei will be discussed. (C) 2001 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.