title: Host AMPK Is a Modulator of Plasmodium Liver Infection.
abstract: 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.
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors: Margarida T Grilo
authors: MTG
authors: Ruivo
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors: Iset Medina
authors: IM
authors: Vera
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors: Joana
authors: J
authors: Sales-Dias
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors: Patrícia
authors: P
authors: Meireles
authors: Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Nil
authors: N
authors: Gural
authors: Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Sangeeta N
authors: SN
authors: Bhatia
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal. Electronic address: mmota@medicina.ulisboa.pt.
authors: Maria M
authors: MM
authors: Mota
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal. Electronic address: lilianamancio@medicina.ulisboa.pt.
authors: Liliana
authors: L
authors: Mancio-Silva
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006790:Host-Parasite Interactions; D006801:Humans; D008018:Life Cycle Stages; D008099:Liver / Q000469:parasitology* / Q000473:pathology; D008288:Malaria / Q000201:enzymology* / Q000469:parasitology* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000254:growth & development / Q000472:pathogenicity
chemical_list: D055372:AMP-Activated Protein Kinases