title: Control of disease tolerance to malaria by nitric oxide and carbon monoxide.
abstract: Nitric oxide (NO) and carbon monoxide (CO) are gasotransmitters that suppress the development of severe forms of malaria associated with Plasmodium infection. Here, we addressed the mechanism underlying their protective effect against experimental cerebral malaria (ECM), a severe form of malaria that develops in Plasmodium-infected mice, which resembles, in many aspects, human cerebral malaria (CM). NO suppresses the pathogenesis of ECM via a mechanism involving (1) the transcription factor nuclear factor erythroid 2-related factor 2 (NRF-2), (2) induction of heme oxygenase-1 (HO-1), and (3) CO production via heme catabolism by HO-1. The protection afforded by NO is associated with inhibition of CD4(+) T helper (TH) and CD8(+) cytotoxic (TC) T cell activation in response to Plasmodium infection via a mechanism involving HO-1 and CO. The protective effect of NO and CO is not associated with modulation of host pathogen load, suggesting that these gasotransmitters establish a crosstalk-conferring disease tolerance to Plasmodium infection.
authors: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors: Viktória
authors: V
authors: Jeney
authors: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors: Susana
authors: S
authors: Ramos
authors: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors: Marie-Louise
authors: ML
authors: Bergman
authors: Faculty of Medicine, Institute of Anatomy, 04103 Leipzig, Germany.
authors: Ingo
authors: I
authors: Bechmann
authors: Faculty of Medicine, Institute of Anatomy, 04103 Leipzig, Germany.
authors: Jasmin
authors: J
authors: Tischer
authors: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors: Ana
authors: A
authors: Ferreira
authors: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors: Virginia
authors: V
authors: Oliveira-Marques
authors: Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors: Chris J
authors: CJ
authors: Janse
authors: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors: Sofia
authors: S
authors: Rebelo
authors: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors: Silvia
authors: S
authors: Cardoso
authors: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal. Electronic address: mpsoares@igc.gulbenkian.pt.
authors: Miguel P
authors: MP
authors: Soares
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002248:Carbon Monoxide / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D016779:Malaria, Cerebral / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology* / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D009569:Nitric Oxide; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1