Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria
Author: ["Ana Pamplona","Ana Ferreira","József Balla","Viktória Jeney","György Balla","Sabrina Epiphanio","Ângelo Chora","Cristina D Rodrigues","Isabel Pombo Gregoire","Margarida Cunha-Rodrigues","Silvia Portugal","Miguel P Soares","Maria M Mota"]
Publication: Nature Medicine
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Abstract
Cerebral malaria claims more than 1 million lives per year. We report that heme oxygenase-1 (HO-1, encoded by Hmox1) prevents the development of experimental cerebral malaria (ECM). BALB/c mice infected with Plasmodium berghei ANKA upregulated HO-1 expression and activity and did not develop ECM. Deletion of Hmox1 and inhibition of HO activity increased ECM incidence to 83% and 78%, respectively. HO-1 upregulation was lower in infected C57BL/6 compared to BALB/c mice, and all infected C57BL/6 mice developed ECM (100% incidence). Pharmacological induction of HO-1 and exposure to the end-product of HO-1 activity, carbon monoxide (CO), reduced ECM incidence in C57BL/6 mice to 10% and 0%, respectively. Whereas neither HO-1 nor CO affected parasitemia, both prevented blood-brain barrier (BBB) disruption, brain microvasculature congestion and neuroinflammation, including CD8+ T-cell brain sequestration. These effects were mediated by the binding of CO to hemoglobin, preventing hemoglobin oxidation and the generation of free heme, a molecule that triggers ECM pathogenesis.
Cite this article
Pamplona, A., Ferreira, A., Balla, J. et al. Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat Med 13, 703–710 (2007). https://doi.org/10.1038/nm1586
