Caspase-1 Activation of Interleukin-1β (IL-1β) and IL-18 Is Dispensable for Induction of Experimental Cerebral Malaria
Caspase-1 Activation of Interleukin-1β (IL-1β) and IL-18 Is Dispensable for Induction of Experimental Cerebral Malaria
复制标题
DOI：
10.1128/iai.05459-11
复制
发表时间：
2011-09-01
影响因子：
3.1
通讯作者：
Hafalla, Julius Clemence R.
中科院分区：
文献类型：
--
作者：
Kordes, Maximilian;Matuschewski, Kai;Hafalla, Julius Clemence R.
疟疾感染是由子孢子侵入肝细胞和肝脏无性繁殖阶段开始的，这些过程被认为是“临床和诊断上沉默的”。裂殖子从肝细胞中排出，以周期性的方式感染红细胞并诱发疾病。宿主的先天免疫系统如何影响疾病的结果以及疟疾期间效应细胞的诱导仍不清楚。同样，肝脏的初始阶段如何影响对血液阶段寄生虫的反应也是未知的。在这里，使用子孢子和血液阶段诱导的感染与啮齿类疟疾寄生虫伯氏疟原虫ANKA，我们表明，MyD 88和Toll样受体2/4（TLR 2/4）途径在实验性脑型疟疾（ECM）的发展中发挥关键作用。引人注目的是，绝对依赖MyD 88和TLR 2/4时，观察到感染开始与子孢子。此外，我们表明，半胱天冬酶-1激活白细胞介素-1 β（IL-1 β）和IL-18，这是与炎症体途径，并没有贡献伯氏疟原虫ANKA诱导的免疫病理学。与这些数据一致，预防性覆盖IL-1 β拮抗剂阿那白滞素并没有降低ECM的发生率。因此，我们认为TLR信号传导功能丧失导致的ECM保护作用是由IL-1 β激活以外的效应机制引起的。
Malaria infection is initiated by sporozoite invasion of hepatocytes and asexual reproduction of liver stages, processes that are regarded to be "clinically and diagnostically silent." Merozoites, which egress from hepatocytes, infect erythrocytes in periodic cycles and induce disease. How the host innate immune system contributes to disease outcomes and to the induction of effector cells during malaria remains unclear. Likewise, how the initial liver stages may shape responses to blood-stage parasites is unknown. Here, using both sporozoite-and blood-stage-induced infections with the rodent malaria parasite Plasmodium berghei ANKA, we show that the MyD88 and Toll-like receptor 2/4 (TLR2/4) pathways play critical roles in the development of experimental cerebral malaria (ECM). Strikingly, an absolute dependence on MyD88 and TLR2/4 was observed when infections were initiated with sporozoites. In addition, we show that caspase-1 activation of interleukin-1 beta (IL-1 beta) and IL-18, which is associated with the inflammasome pathway, does not contribute to P. berghei ANKA-induced immunopathology. Consistent with these data, prophylactic cover with the IL-1 beta antagonist anakinra did not reduce the incidence of ECM. Therefore, we propose that protection against ECM due to loss of TLR signaling functions is caused by effector mechanisms other than IL-1 beta activation.