文章基本信息

标题：Renal control of disease tolerance to malaria
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作者：Susana Ramos ; Ana Rita Carlos ; Balamurugan Sundaram 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：12
页码：5681-5686
DOI：10.1073/pnas.1822024116
出版社：The National Academy of Sciences of the United States of America
摘要：Malaria, the disease caused by Plasmodium spp. infection, remains a major global cause of morbidity and mortality. Host protection from malaria relies on immune-driven resistance mechanisms that kill Plasmodium . However, these mechanisms are not sufficient per se to avoid the development of severe forms of disease. This is accomplished instead via the establishment of disease tolerance to malaria, a defense strategy that does not target Plasmodium directly. Here we demonstrate that the establishment of disease tolerance to malaria relies on a tissue damage-control mechanism that operates specifically in renal proximal tubule epithelial cells (RPTEC). This protective response relies on the induction of heme oxygenase-1 ( HMOX1 ; HO-1) and ferritin H chain ( FTH ) via a mechanism that involves the transcription-factor nuclear-factor E2-related factor-2 ( NRF2 ). As it accumulates in plasma and urine during the blood stage of Plasmodium infection, labile heme is detoxified in RPTEC by HO-1 and FTH, preventing the development of acute kidney injury, a clinical hallmark of severe malaria.
关键词：infection ; malaria ; disease tolerance ; heme ; kidney