title: Host cell autophagy contributes to Plasmodium liver development.
abstract: Autophagy plays an important role in the defence against intracellular pathogens. However, some microorganisms can manipulate this host cell pathway to their advantage. In this study, we addressed the role of host cell autophagy during Plasmodium berghei liver infection. We show that vesicles containing the autophagic marker LC3 surround parasites from early time-points after invasion and throughout infection and colocalize with the parasitophorous vacuole membrane. Moreover, we show that the LC3-positive vesicles that surround Plasmodium parasites are amphisomes that converge from the endocytic and autophagic pathways, because they contain markers of both pathways. When the host autophagic pathway was inhibited by silencing several of its key regulators such as LC3, Beclin1, Vps34 or Atg5, we observed a reduction in parasite size. We also found that LC3 surrounds parasites in vivo and that parasite load is diminished in a mouse model deficient for autophagy. Together, these results show the importance of the host autophagic pathway for parasite development during the liver stage of Plasmodium infection.
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
authors.forename: Carolina
authors.initials: C
authors.lastname: Thieleke-Matos
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Lopes da Silva
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
authors.forename: Laura
authors.initials: L
authors.lastname: Cabrita-Santos
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.
authors.forename: Martim D
authors.initials: MD
authors.lastname: Portal
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.
authors.forename: Inês P
authors.initials: IP
authors.lastname: Rodrigues
authors.affiliation: Malaria Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Zuzarte-Luis
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.
authors.forename: José S
authors.initials: JS
authors.lastname: Ramalho
authors.affiliation: Institute of Ophthalmology, University College London, London, EC1V 9EL, UK.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Futter
authors.affiliation: Malaria Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.
authors.forename: Duarte C
authors.initials: DC
authors.lastname: Barral
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.|Molecular Medicine Section, National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D006790:Host-Parasite Interactions / Q000502:physiology*; D008099:Liver / Q000469:parasitology* / Q000473:pathology; D008288:Malaria / Q000469:parasitology / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010962:Plasmodium berghei / Q000472:pathogenicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins