Host AMPK Is a Modulator of Plasmodium Liver Infection
Manipulation of the master regulator of energy homeostasis AMP-activated protein kinase (AMPK) activity is a strategy used by many intracellular pathogens for successful replication. Infection by most pathogens leads to an activation of host AMPK activity due to the energetic demands placed on the i...
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doaj-96f97c3fa6cb409b84c49c9a66d0a99d2020-11-24T21:29:06ZengElsevierCell Reports2211-12472016-09-0116102539254510.1016/j.celrep.2016.08.001Host AMPK Is a Modulator of Plasmodium Liver InfectionMargarida T. Grilo Ruivo0Iset Medina Vera1Joana Sales-Dias2Patrícia Meireles3Nil Gural4Sangeeta N. Bhatia5Maria M. Mota6Liliana Mancio-Silva7Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, PortugalDepartment of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USADepartment of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USAInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, PortugalManipulation of the master regulator of energy homeostasis AMP-activated protein kinase (AMPK) activity is a strategy used by many intracellular pathogens for successful replication. Infection by most pathogens leads to an activation of host AMPK activity due to the energetic demands placed on the infected cell. Here, we demonstrate that the opposite is observed in cells infected with rodent malaria parasites. Indeed, AMPK activity upon the infection of hepatic cells is suppressed and dispensable for successful infection. By contrast, an overactive AMPK is deleterious to intracellular growth and replication of different Plasmodium spp., including the human malaria parasite, P. falciparum. The negative impact of host AMPK activity on infection was further confirmed in mice under conditions that activate its function. Overall, this work establishes the role of host AMPK signaling as a suppressive pathway of Plasmodium hepatic infection and as a potential target for host-based antimalarial interventions.http://www.sciencedirect.com/science/article/pii/S2211124716310312 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Margarida T. Grilo Ruivo Iset Medina Vera Joana Sales-Dias Patrícia Meireles Nil Gural Sangeeta N. Bhatia Maria M. Mota Liliana Mancio-Silva |
spellingShingle |
Margarida T. Grilo Ruivo Iset Medina Vera Joana Sales-Dias Patrícia Meireles Nil Gural Sangeeta N. Bhatia Maria M. Mota Liliana Mancio-Silva Host AMPK Is a Modulator of Plasmodium Liver Infection Cell Reports |
author_facet |
Margarida T. Grilo Ruivo Iset Medina Vera Joana Sales-Dias Patrícia Meireles Nil Gural Sangeeta N. Bhatia Maria M. Mota Liliana Mancio-Silva |
author_sort |
Margarida T. Grilo Ruivo |
title |
Host AMPK Is a Modulator of Plasmodium Liver Infection |
title_short |
Host AMPK Is a Modulator of Plasmodium Liver Infection |
title_full |
Host AMPK Is a Modulator of Plasmodium Liver Infection |
title_fullStr |
Host AMPK Is a Modulator of Plasmodium Liver Infection |
title_full_unstemmed |
Host AMPK Is a Modulator of Plasmodium Liver Infection |
title_sort |
host ampk is a modulator of plasmodium liver infection |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-09-01 |
description |
Manipulation of the master regulator of energy homeostasis AMP-activated protein kinase (AMPK) activity is a strategy used by many intracellular pathogens for successful replication. Infection by most pathogens leads to an activation of host AMPK activity due to the energetic demands placed on the infected cell. Here, we demonstrate that the opposite is observed in cells infected with rodent malaria parasites. Indeed, AMPK activity upon the infection of hepatic cells is suppressed and dispensable for successful infection. By contrast, an overactive AMPK is deleterious to intracellular growth and replication of different Plasmodium spp., including the human malaria parasite, P. falciparum. The negative impact of host AMPK activity on infection was further confirmed in mice under conditions that activate its function. Overall, this work establishes the role of host AMPK signaling as a suppressive pathway of Plasmodium hepatic infection and as a potential target for host-based antimalarial interventions. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716310312 |
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