Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection
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...
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doaj-00f86738c4ce49d991978770198f903a2020-11-25T00:23:36ZengBMCMalaria Journal1475-28752018-07-0117111310.1186/s12936-018-2410-6Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infectionAugustina Frimpong0Kwadwo Asamoah Kusi1Bernard Tornyigah2Michael Fokuo Ofori3Wilfred Ndifon4West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of GhanaImmunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of GhanaAfrican Institute for Mathematical SciencesAbstract 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.http://link.springer.com/article/10.1186/s12936-018-2410-6MalariaRegulatory T-cellsT-cell activationAsymptomaticSymptomaticChildren |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Augustina Frimpong Kwadwo Asamoah Kusi Bernard Tornyigah Michael Fokuo Ofori Wilfred Ndifon |
spellingShingle |
Augustina Frimpong Kwadwo Asamoah Kusi Bernard Tornyigah Michael Fokuo Ofori Wilfred Ndifon Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection Malaria Journal Malaria Regulatory T-cells T-cell activation Asymptomatic Symptomatic Children |
author_facet |
Augustina Frimpong Kwadwo Asamoah Kusi Bernard Tornyigah Michael Fokuo Ofori Wilfred Ndifon |
author_sort |
Augustina Frimpong |
title |
Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection |
title_short |
Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection |
title_full |
Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection |
title_fullStr |
Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection |
title_full_unstemmed |
Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection |
title_sort |
characterization of t cell activation and regulation in children with asymptomatic plasmodium falciparum infection |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2018-07-01 |
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. |
topic |
Malaria Regulatory T-cells T-cell activation Asymptomatic Symptomatic Children |
url |
http://link.springer.com/article/10.1186/s12936-018-2410-6 |
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