Natural measles causes prolonged suppression of interleukin-12 production
Natural measles causes prolonged suppression of interleukin-12 production
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DOI：
10.1086/321009
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发表时间：
2001-07-01
影响因子：
6.4
通讯作者：
Karp, CL
中科院分区：
文献类型：
--
作者：
Atabani, SF;Byrnes, AA;Karp, CL
在疫苗可预防的疾病中，麻疹是全世界儿童的头号杀手。麻疹病毒（MV）感染与细胞介导的免疫反应的长期抑制有关，这一现象被认为是继发性感染易感性的基础，继发性感染是导致大多数麻疹相关死亡的原因。白细胞介素(IL)-12对细胞免疫的协调至关重要。在体外，MV通过与CD46（一种补体调节蛋白，是一种MV受体）结合，特异性地抑制单核细胞/巨噬细胞产生IL-12。为了解决MV对体内IL-12反应的影响，在冈比亚麻疹患者中检测了细胞因子的产生。这些患者外周血单核细胞产生的IL-12明显受到抑制，这为许多与麻疹相关的免疫异常提供了统一的机制。这种抑制是长期的，在急性感染恢复几个月后，IL-12产生明显的刺激特异性抑制。然而，尽管有这种抑制，IL-12的响应性仍然保持不变。
Among vaccine-preventable diseases, measles is the preeminent killer of children worldwide. Infection with measles virus (MV) is associated with prolonged suppression of cell-mediated immune responses, a phenomenon that is thought to underlie the susceptibility to secondary infections that accounts for most measles-related mortality. Interleukin (IL)-12 is critical for the orchestration of cellular immunity. MV specifically ablates IL-12 production by monocyte/macrophages in vitro through binding to CD46, a complement regulatory protein that is an MV receptor. To address the effect of MV on IL-12 responses in vivo, cytokine production was examined in Gambian patients with measles. IL-12 production by peripheral blood monocytes from such patients is markedly suppressed, which provides a unifying mechanism for many of the immunologic abnormalities associated with measles. This suppression is prolonged, with significant, stimulus-specific inhibition of IL-12 production demonstrable months after recovery from acute infection. However, despite this suppression, IL-12 responsiveness remains intact.