Renal control of disease tolerance to malaria.
Susana Ramos,Ana Rita Carlos,Balamurugan Sundaram,Viktória Jeney,Ana Ribeiro,Raffaella Gozzelino,Claudia Bank,Erida Gjini,Faouzi Braza,Rui Martins,Temitope W. Ademolue,Birte Blankenhaus,Zélia Gouveia,Pedro Faísca,Damian L. Trujillo,Silvia Cardoso,Sofia Rebelo,Laura del Barrio,Abolfazl Zarjou,Subhashini Bolisetty,Anupam Agarwal,Anupam Agarwal,Miguel P. Soares +22 more
TLDR
It is demonstrated 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), which relies on the induction of heme oxygenase-1 and ferritin H chain via a mechanism that involves the transcription-factor nuclear-factor E2-related factor-2 (NRF2).Abstract:
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.read more
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The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway.
Liam Baird,Masayuki Yamamoto +1 more
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Iron in infection and immunity.
Manfred Nairz,Günter Weiss +1 more
TL;DR: This review highlights the most important interconnections between iron metabolism and immunity, focusing on host defense against relevant infections and on the clinical consequences of anemia of inflammation.
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Neutrophil extracellular traps drive inflammatory pathogenesis in malaria
Sebastian Lorenz Knackstedt,Athina Georgiadou,Falko Apel,Ulrike Abu-Abed,Christopher A. Moxon,Christopher A. Moxon,Aubrey J. Cunnington,Bärbel Raupach,Deirdre Cunningham,Jean Langhorne,Renate Krüger,Valentina Barrera,Simon P. Harding,Aase Berg,Sam Patel,Kari Otterdal,Benjamin Mordmüller,Evelin Schwarzer,Volker Brinkmann,Arturo Zychlinsky,Borko Amulic,Borko Amulic +21 more
TL;DR: It is demonstrated that neutrophils have a key role in malaria immunopathology and proposed inhibition of NETs as a treatment strategy in vascular infections and shown that heme-induced NETs are essential for malaria pathogenesis.
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Mechanisms of haemolysis-induced kidney injury.
TL;DR: These mechanisms are not sufficient to avoid pathological outcomes instigated by cell-free haemoglobin, haem and iron during haemolytic conditions such as oxidative stress, nitric oxide depletion, inflammation and cell death.
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Pro-inflammatory Actions of Heme and Other Hemoglobin-Derived DAMPs
Marcelo T. Bozza,Viktória Jeney +1 more
TL;DR: This review aims to summarize the current knowledge about the formation and pro-inflammatory actions of heme and other Hb-derived DAMPs.
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