RRC ID 32236
Author Jeney V, Ramos S, Bergman ML, Bechmann I, Tischer J, Ferreira A, Oliveira-Marques V, Janse CJ, Rebelo S, Cardoso S, Soares MP.
Title Control of disease tolerance to malaria by nitric oxide and carbon monoxide.
Journal Cell Rep
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.
Volume 8(1)
Pages 126-36
Published 2014-7-10
DOI 10.1016/j.celrep.2014.05.054
PII S2211-1247(14)00448-3
PMID 24981859
MeSH Animals CD8-Positive T-Lymphocytes / drug effects CD8-Positive T-Lymphocytes / immunology Carbon Monoxide / metabolism Carbon Monoxide / pharmacology* Carbon Monoxide / therapeutic use Heme Oxygenase-1 / genetics Heme Oxygenase-1 / metabolism Immune Tolerance* Lymphocyte Activation Malaria, Cerebral / drug therapy Malaria, Cerebral / immunology* Mice Mice, Inbred C57BL NF-E2-Related Factor 2 / genetics NF-E2-Related Factor 2 / metabolism Nitric Oxide / pharmacology* Nitric Oxide / therapeutic use T-Lymphocytes, Cytotoxic / drug effects T-Lymphocytes, Cytotoxic / immunology T-Lymphocytes, Helper-Inducer / drug effects T-Lymphocytes, Helper-Inducer / immunology
IF 8.109
Times Cited 39
Mice RBRC01390