title: Hepatocyte growth factor and its receptor are required for malaria infection.
abstract: Plasmodium, the causative agent of malaria, must first infect hepatocytes to initiate a mammalian infection. Sporozoites migrate through several hepatocytes, by breaching their plasma membranes, before infection is finally established in one of them. Here we show that wounding of hepatocytes by sporozoite migration induces the secretion of hepatocyte growth factor (HGF), which renders hepatocytes susceptible to infection. Infection depends on activation of the HGF receptor, MET, by secreted HGF. The malaria parasite exploits MET not as a primary binding site, but as a mediator of signals that make the host cell susceptible to infection. HGF/MET signaling induces rearrangements of the host-cell actin cytoskeleton that are required for the early development of the parasites within hepatocytes. Our findings identify HGF and MET as potential targets for new approaches to malaria prevention.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Carrolo
authors.forename: Silvia
authors.initials: S
authors.lastname: Giordano
authors.forename: Laura
authors.initials: L
authors.lastname: Cabrita-Santos
authors.forename: Simona
authors.initials: S
authors.lastname: Corso
authors.forename: Ana M
authors.initials: AM
authors.lastname: Vigário
authors.forename: Susana
authors.initials: S
authors.lastname: Silva
authors.forename: Patricia
authors.initials: P
authors.lastname: Leirião
authors.forename: Daniel
authors.initials: D
authors.lastname: Carapau
authors.forename: Rosario
authors.initials: R
authors.lastname: Armas-Portela
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Comoglio
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D008288:Malaria / Q000378:metabolism*; D051379:Mice; D010961:Plasmodium / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met