KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria

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

doi:10.1038/s41598-019-42782-x

KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria

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

Research output: Contribution to journal › Article › Research › peer-review

3 Citations (Scopus)

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 language	English
Article number	6356
Number of pages	11
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-42782-x
Publication status	Published - 1 Dec 2019

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273460584-oaFinal published version, 2.06 MBLicence: CC BY

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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. ",

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AU - Hortle, Elinor

AU - Starrs, Lora

AU - Brown, Fiona C.

AU - Jane, Stephen M.

AU - Curtis, David J.

AU - McMorran, Brendan J.

AU - Foote, Simon J.

AU - Burgio, Gaetan

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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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KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria

Abstract

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Author Correction: KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria (Scientific Reports, (2019), 9, 1, (6356), 10.1038/s41598-019-42782-x)

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