Renal control of disease tolerance to malaria

Susana Ramos, Ana Rita Carlos, Balamurugan Sundaram, V. Jeney, Ana Ribeiro, Raffaella Gozzelino, Claudia Bank, Erida Gjini, Faouzi Braza, Rui Martins, Temitope Wilson Ademolue, Birte Blankenhaus, Zélia Gouveia, Pedro Faísca, Damian Trujillo, Sílvia Cardoso, Sofia Rebelo, Laura del Barrio, Abolfazl Zarjou, Subhashini Bolisetty & 2 others Anupam Agarwal, Miguel P. Soares

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)5681-5686
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number12
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Malaria
Kidney
Plasmodium
Apoferritins
Proximal Kidney Tubule
Epithelial Cells
NF-E2-Related Factor 2
Heme Oxygenase-1
Heme
Acute Kidney Injury
Transcription Factors
Urine
Morbidity
Mortality
Infection

Keywords

  • Disease tolerance
  • Heme
  • Infection
  • Kidney
  • Malaria

ASJC Scopus subject areas

  • General

Cite this

Ramos, S., Carlos, A. R., Sundaram, B., Jeney, V., Ribeiro, A., Gozzelino, R., ... Soares, M. P. (2019). Renal control of disease tolerance to malaria. Proceedings of the National Academy of Sciences of the United States of America, 116(12), 5681-5686. https://doi.org/10.1073/pnas.1822024116

Renal control of disease tolerance to malaria. / Ramos, Susana; Carlos, Ana Rita; Sundaram, Balamurugan; Jeney, V.; Ribeiro, Ana; Gozzelino, Raffaella; Bank, Claudia; Gjini, Erida; Braza, Faouzi; Martins, Rui; Ademolue, Temitope Wilson; Blankenhaus, Birte; Gouveia, Zélia; Faísca, Pedro; Trujillo, Damian; Cardoso, Sílvia; Rebelo, Sofia; del Barrio, Laura; Zarjou, Abolfazl; Bolisetty, Subhashini; Agarwal, Anupam; Soares, Miguel P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 12, 01.01.2019, p. 5681-5686.

Research output: Contribution to journalArticle

Ramos, S, Carlos, AR, Sundaram, B, Jeney, V, Ribeiro, A, Gozzelino, R, Bank, C, Gjini, E, Braza, F, Martins, R, Ademolue, TW, Blankenhaus, B, Gouveia, Z, Faísca, P, Trujillo, D, Cardoso, S, Rebelo, S, del Barrio, L, Zarjou, A, Bolisetty, S, Agarwal, A & Soares, MP 2019, 'Renal control of disease tolerance to malaria', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 12, pp. 5681-5686. https://doi.org/10.1073/pnas.1822024116
Ramos, Susana ; Carlos, Ana Rita ; Sundaram, Balamurugan ; Jeney, V. ; Ribeiro, Ana ; Gozzelino, Raffaella ; Bank, Claudia ; Gjini, Erida ; Braza, Faouzi ; Martins, Rui ; Ademolue, Temitope Wilson ; Blankenhaus, Birte ; Gouveia, Zélia ; Faísca, Pedro ; Trujillo, Damian ; Cardoso, Sílvia ; Rebelo, Sofia ; del Barrio, Laura ; Zarjou, Abolfazl ; Bolisetty, Subhashini ; Agarwal, Anupam ; Soares, Miguel P. / Renal control of disease tolerance to malaria. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 12. pp. 5681-5686.
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