KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria

Elinor Hortle, Lora Starrs, Fiona Brown, Stephen Jane, David Curtis, Brendan J. McMorran, Simon J. Foote, Gaetan Burgio

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Article number6356
Number of pages11
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

Hortle, Elinor ; Starrs, Lora ; Brown, Fiona ; Jane, Stephen ; Curtis, David ; McMorran, Brendan J. ; Foote, Simon J. ; Burgio, Gaetan. / KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria. / Hortle, Elinor; Starrs, Lora; Brown, Fiona; Jane, Stephen; Curtis, David; McMorran, Brendan J.; Foote, Simon J.; Burgio, Gaetan.

In: Scientific Reports, Vol. 9, No. 1, 6356, 01.12.2019.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Hortle, Elinor

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AB - 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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