Murine cerebral malaria development is independent of Toll-like receptor signaling
Murine cerebral malaria development is independent of Toll-like receptor signaling
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DOI：
10.2353/ajpath.2007.060889
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发表时间：
2007-05-01
影响因子：
6
通讯作者：
Ryffel, Bernhard
中科院分区：
文献类型：
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作者：
Togbe, Dieudonnee;Schofield, Louis;Ryffel, Bernhard
据报道，疟疾色素疟原虫色素可通过 Toll 样受体 (TLR)-9 的参与激活先天免疫。然而，TLR 激活在脑型疟疾 (CM)（人类疟疾感染的致命并发症）发展中的作用尚不清楚。使用小鼠中的伯氏疟原虫 ANKA (PbA) 感染作为 CM 模型，我们在此报告，TLR9 缺陷的小鼠无法免受 CM 的影响。为了排除 TLR 家族其他成员在 PbA 识别中的作用，我们感染了单个 TLR1、-2、-3、-4、-6、-7 或 -9 及其接头蛋白 MyD88、TIRAP 和 TRIF 缺陷的小鼠。与对 CM 具有抗性的淋巴毒素 a 缺陷小鼠相比，所有 TLR 缺陷小鼠与野生型对照小鼠一样对致命的 CM 发展敏感，并出现典型的微血管损伤，伴有脑部和肺部血管渗漏和出血，以及类似的寄生虫血症、血小板减少症、中性粒细胞增多症和淋巴细胞减少症。总之，目前的数据并不排除疟疾分子基序可能激活先天免疫系统的可能性。然而，TLR 依赖性先天免疫激活不太可能对 PbA 感染的促炎反应和致命性 CM 的发展产生显着影响。
Malaria pigment hemozoin was reported to activate the innate immunity by Toll-like receptor (TLR)-9 engagement. However, the role of TLR activation for the development of cerebral malaria (CM), a lethal complication of malaria infection in humans, is unknown. Using Plasmodium berghei ANKA (PbA) infection in mice as a model of CM, we report here that TLR9-deficient mice are not protected from CM. To exclude the role of other members of the TLR family in PbA recognition, we infected mice deficient for single TLR1, -2, -3, -4, -6, -7, or -9 and their adapter proteins MyD88, TIRAP, and TRIF. In contrast to lymphotoxin a-deficient mice, which are resistant to CM, all TLR-deficient mice were as sensitive to fatal CM development as wild-type control mice and developed typical microvascular damage with vascular leak and hemorrhage in the brain and lung, together with comparable parasitemia, thrombocytopenia, neutrophilia, and lymphopenia. In conclusion, the present data do not exclude the possibility that malarial molecular motifs may activate the innate immune system. However, TLR-dependent activation of innate immunity is unlikely to contribute significantly to the proinflammatory response to PbA infection and the development of fatal CM.