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KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria

Plasmodium falciparum malaria causes half a million deaths per year, with up to 9% of this mortality caused by cerebral malaria (CM). One of the major processes contributing to the development of CM is an excess of host inflammatory cytokines. Recently K+ signaling has emerged as an important mediat...

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Autores principales: Hortle, Elinor, Starrs, Lora, Brown, Fiona C., Jane, Stephen M., Curtis, David J., McMorran, Brendan J., Foote, Simon J., Burgio, Gaetan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478876/
https://www.ncbi.nlm.nih.gov/pubmed/31015511
http://dx.doi.org/10.1038/s41598-019-42782-x
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author Hortle, Elinor
Starrs, Lora
Brown, Fiona C.
Jane, Stephen M.
Curtis, David J.
McMorran, Brendan J.
Foote, Simon J.
Burgio, Gaetan
author_facet Hortle, Elinor
Starrs, Lora
Brown, Fiona C.
Jane, Stephen M.
Curtis, David J.
McMorran, Brendan J.
Foote, Simon J.
Burgio, Gaetan
author_sort Hortle, Elinor
collection PubMed
description Plasmodium falciparum malaria causes half a million deaths per year, with up to 9% of this mortality caused by cerebral malaria (CM). One of the major processes contributing to the development of CM is an excess of host inflammatory cytokines. Recently K+ signaling has emerged as an important mediator of the inflammatory response to infection; we therefore investigated whether mice carrying an ENU induced activation of the electroneutral K+ channel KCC1 had an altered response to Plasmodium berghei. Here we show that Kcc1(M935K/M935K) mice are protected from the development of experimental cerebral malaria, and that this protection is associated with an increased CD4+ and TNFa response. This is the first description of a K+ channel affecting the development of experimental cerebral malaria.
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spelling pubmed-64788762019-05-03 KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria Hortle, Elinor Starrs, Lora Brown, Fiona C. Jane, Stephen M. Curtis, David J. McMorran, Brendan J. Foote, Simon J. Burgio, Gaetan Sci Rep Article Plasmodium falciparum malaria causes half a million deaths per year, with up to 9% of this mortality caused by cerebral malaria (CM). One of the major processes contributing to the development of CM is an excess of host inflammatory cytokines. Recently K+ signaling has emerged as an important mediator of the inflammatory response to infection; we therefore investigated whether mice carrying an ENU induced activation of the electroneutral K+ channel KCC1 had an altered response to Plasmodium berghei. Here we show that Kcc1(M935K/M935K) mice are protected from the development of experimental cerebral malaria, and that this protection is associated with an increased CD4+ and TNFa response. This is the first description of a K+ channel affecting the development of experimental cerebral malaria. Nature Publishing Group UK 2019-04-23 /pmc/articles/PMC6478876/ /pubmed/31015511 http://dx.doi.org/10.1038/s41598-019-42782-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hortle, Elinor
Starrs, Lora
Brown, Fiona C.
Jane, Stephen M.
Curtis, David J.
McMorran, Brendan J.
Foote, Simon J.
Burgio, Gaetan
KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria
title KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria
title_full KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria
title_fullStr KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria
title_full_unstemmed KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria
title_short KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria
title_sort kcc1 activation protects mice from the development of experimental cerebral malaria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478876/
https://www.ncbi.nlm.nih.gov/pubmed/31015511
http://dx.doi.org/10.1038/s41598-019-42782-x
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