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...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2018
|
Subjects: | |
Online Access: | https://doi.org/10.1186/s12936-018-2410-6 https://doaj.org/article/00f86738c4ce49d991978770198f903a |
id |
ftdoajarticles:oai:doaj.org/article:00f86738c4ce49d991978770198f903a |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:00f86738c4ce49d991978770198f903a 2023-05-15T15:15:23+02:00 Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection Augustina Frimpong Kwadwo Asamoah Kusi Bernard Tornyigah Michael Fokuo Ofori Wilfred Ndifon 2018-07-01T00:00:00Z https://doi.org/10.1186/s12936-018-2410-6 https://doaj.org/article/00f86738c4ce49d991978770198f903a EN eng BMC http://link.springer.com/article/10.1186/s12936-018-2410-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2410-6 1475-2875 https://doaj.org/article/00f86738c4ce49d991978770198f903a Malaria Journal, Vol 17, Iss 1, Pp 1-13 (2018) Malaria Regulatory T-cells T-cell activation Asymptomatic Symptomatic Children Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2018 ftdoajarticles https://doi.org/10.1186/s12936-018-2410-6 2022-12-31T02:55:10Z 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 ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 17 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Malaria Regulatory T-cells T-cell activation Asymptomatic Symptomatic Children Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Regulatory T-cells T-cell activation Asymptomatic Symptomatic Children Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 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 |
topic_facet |
Malaria Regulatory T-cells T-cell activation Asymptomatic Symptomatic Children Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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 ... |
format |
Article in Journal/Newspaper |
author |
Augustina Frimpong Kwadwo Asamoah Kusi Bernard Tornyigah Michael Fokuo Ofori Wilfred Ndifon |
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 |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12936-018-2410-6 https://doaj.org/article/00f86738c4ce49d991978770198f903a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 17, Iss 1, Pp 1-13 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12936-018-2410-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2410-6 1475-2875 https://doaj.org/article/00f86738c4ce49d991978770198f903a |
op_doi |
https://doi.org/10.1186/s12936-018-2410-6 |
container_title |
Malaria Journal |
container_volume |
17 |
container_issue |
1 |
_version_ |
1766345749305491456 |