Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection

Show simple item record Frimpong, A. Kusi, K.A. Tornyigah, B. Ofori, M.F. Ndifon, W. 2019-07-03T09:59:41Z 2019-07-03T09:59:41Z 2018-07
dc.description.abstract Background Asymptomatic Plasmodium infections are characterized by the absence of clinical disease and the ability to restrict parasite replication. Increasing levels of regulatory T cells (Tregs) in Plasmodium falciparum infections have been associated with the risk of developing clinical disease, suggesting that individuals with asymptomatic infections may have reduced Treg frequency. However, the relationship between Tregs, cellular activation and parasite control in asymptomatic malaria remains unclear. Methods In a cross-sectional study, the levels of Tregs and other T cell activation phenotypes were compared using flow cytometry in symptomatic, asymptomatic and uninfected children before and after stimulation with infected red blood cell lysates (iRBCs). In addition, the association between these T cell phenotypes and parasitaemia were investigated. Results In children with asymptomatic infections, levels of Tregs and activated T cells were comparable to those in healthy controls but significantly lower than those in symptomatic children. After iRBC stimulation, levels of Tregs remained lower for asymptomatic versus symptomatic children. In contrast, levels of activated T cells were higher for asymptomatic children. Strikingly, the pre-stimulation levels of two T cell activation phenotypes (CD8+CD69+ and CD8+CD25+CD69+) and the post-stimulation levels of two regulatory phenotypes (CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+) were significantly positively correlated with and explained 68% of the individual variation in parasitaemia. A machine-learning model based on levels of these four phenotypes accurately distinguished between asymptomatic and symptomatic children (sensitivity = 86%, specificity = 94%), suggesting that these phenotypes govern the observed variation in disease status. Conclusion Compared to symptomatic P. falciparum infections, in children asymptomatic infections are characterized by lower levels of Tregs and activated T cells, which are associated with lower parasitaemia. The results indicate that T cell regulatory and activation phenotypes govern both parasitaemia and disease status in paediatric malaria in the studied sub-Saharan African population. en_US
dc.language.iso en en_US
dc.publisher Malaria Journal en_US
dc.subject Malaria en_US
dc.subject Regulatory T-cells en_US
dc.subject T-cell activation en_US
dc.subject Asymptomatic en_US
dc.subject Symptomatic en_US
dc.subject Children en_US
dc.subject Falciparum en_US
dc.subject Immunity en_US
dc.title Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection en_US
dc.type Article en_US

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