Sickle hemoglobin confers tolerance to plasmodium infection

Ana Ferreira, Ivo Marguti, Ingo Bechmann, V. Jeney, Ângelo Chora, Nuno R. Palha, Sofia Rebelo, Annie Henri, Yves Beuzard, Miguel P. Soares

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

Sickle human hemoglobin (Hb) confers a survival advantage to individuals living in endemic areas of malaria, the disease caused by Plasmodium infection. As demonstrated hereby, mice expressing sickle Hb do not succumb to experimental cerebral malaria (ECM). This protective effect is exerted irrespectively of parasite load, revealing that sickle Hb confers host tolerance to Plasmodium infection. Sickle Hb induces the expression of heme oxygenase-1 (HO-1) in hematopoietic cells, via a mechanism involving the transcription factor NF-E2-related factor 2 (Nrf2). Carbon monoxide (CO), a byproduct of heme catabolism by HO-1, prevents further accumulation of circulating free heme after Plasmodium infection, suppressing the pathogenesis of ECM. Moreover, sickle Hb inhibits activation and/or expansion of pathogenic CD8+ T cells recognizing antigens expressed by Plasmodium, an immunoregulatory effect that does not involve Nrf2 and/or HO-1. Our findings provide insight into molecular mechanisms via which sickle Hb confers host tolerance to severe forms of malaria.

Original languageEnglish
Pages (from-to)398-409
Number of pages12
JournalCell
Volume145
Issue number3
DOIs
Publication statusPublished - Apr 29 2011

Fingerprint

Sickle Hemoglobin
Malaria
Heme Oxygenase-1
NF-E2-Related Factor 2
Cerebral Malaria
Heme
Transcription factors
T-cells
Parasite Load
Carbon Monoxide
Plasmodium
Byproducts
Hemoglobins
Chemical activation
Transcription Factors
Antigens
T-Lymphocytes
Survival

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ferreira, A., Marguti, I., Bechmann, I., Jeney, V., Chora, Â., Palha, N. R., ... Soares, M. P. (2011). Sickle hemoglobin confers tolerance to plasmodium infection. Cell, 145(3), 398-409. https://doi.org/10.1016/j.cell.2011.03.049

Sickle hemoglobin confers tolerance to plasmodium infection. / Ferreira, Ana; Marguti, Ivo; Bechmann, Ingo; Jeney, V.; Chora, Ângelo; Palha, Nuno R.; Rebelo, Sofia; Henri, Annie; Beuzard, Yves; Soares, Miguel P.

In: Cell, Vol. 145, No. 3, 29.04.2011, p. 398-409.

Research output: Contribution to journalArticle

Ferreira, A, Marguti, I, Bechmann, I, Jeney, V, Chora, Â, Palha, NR, Rebelo, S, Henri, A, Beuzard, Y & Soares, MP 2011, 'Sickle hemoglobin confers tolerance to plasmodium infection', Cell, vol. 145, no. 3, pp. 398-409. https://doi.org/10.1016/j.cell.2011.03.049
Ferreira A, Marguti I, Bechmann I, Jeney V, Chora Â, Palha NR et al. Sickle hemoglobin confers tolerance to plasmodium infection. Cell. 2011 Apr 29;145(3):398-409. https://doi.org/10.1016/j.cell.2011.03.049
Ferreira, Ana ; Marguti, Ivo ; Bechmann, Ingo ; Jeney, V. ; Chora, Ângelo ; Palha, Nuno R. ; Rebelo, Sofia ; Henri, Annie ; Beuzard, Yves ; Soares, Miguel P. / Sickle hemoglobin confers tolerance to plasmodium infection. In: Cell. 2011 ; Vol. 145, No. 3. pp. 398-409.
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