Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy
Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy
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DOI：
10.1172/jci10182
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发表时间：
2000-10-01
影响因子：
15.9
通讯作者：
Bentwich, Z
中科院分区：
文献类型：
--
作者：
Borkow, G;Leng, QB;Bentwich, Z
蠕虫寄生虫会引起人类广泛、持续的感染。埃塞俄比亚人移民到以色列（这里用“Eth.”表示），其中许多人感染了蠕虫并处于慢性免疫激活状态，这使我们能够研究这种免疫激活对免疫反应的影响。我们研究了 190 Eth 的免疫特征和免疫功能。和以色列非伦理。 (Isr.) 高度、部分或非免疫激活的个体。来自高度免疫激活个体的免疫细胞在几种信号反应中存在缺陷，所有这些信号反应在抗蠕虫治疗后逐渐恢复。从各种酪氨酸激酶和 MAPK 激酶、ERK1/2 和 p38 的磷酸化可以看出，这些细胞的跨膜信号传导较差；磷酸化 I kappa B α 的降解不足；细胞毒性 T 淋巴细胞相关抗原 4 (CTLA-4) 的表达增加，这似乎会阻止这些细胞的增殖反应；刺激后CD8(+)细胞分泌β-趋化因子减少；并减少增殖以回忆抗原刺激。高度免疫激活的个体在驱虫前也表现出延迟型皮肤超敏反应，以回忆抗原。这些发现支持这样的观点，即慢性蠕虫感染会导致持续的免疫激活，从而导致反应低下和无反应。这种受损的免疫功能可能会降低这些个体应对感染和接种疫苗后产生细胞保护性免疫力的能力。
Helminthic parasites cause widespread, persistent infections in humans. The immigration of Ethiopians to Israel (a group denoted here by "Eth."), many of them infested with helminths and in a chronic immune-activation state, enabled us to investigate the effects of such immune activation on immune responses. We studied the immune profile and immune functions of 190 Eth. and Israeli non-Eth. (Isr.) highly, partially, or non-immune-activated individuals. Immune cells from highly immune-activated individuals were defective in several signaling responses, all of which were restored gradually following anti-helminthic treatment. These cells showed poor transmembrane signaling, as seen by the phosphorylation of various tyrosine kinases and of the MAPK kinases, ERK1/2 and p38; deficient degradation of phosphorylated I kappa B alpha; increased expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), which appears to block proliferative responses in these cells; decreased beta-chemokine secretion by CD8(+) cells after stimulation; and reduced proliferation to recall antigen stimulation. Highly immune-activated individuals also showed decreased delayed-type skin hypersensitivity responses to recall antigen before deworming. These findings support the notion that chronic helminthic infections cause persistent immune activation that results in hyporesponsiveness and anergy. Such impaired immune functions may diminish the capacity of these individuals to cope with infections and to generate cellular protective immunity after vaccination.