Hepatocyte growth factor and its receptor are required for malaria infection.
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.
Carrolo
Margarida
M
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
Giordano
Silvia
S
Cabrita-Santos
Laura
L
Corso
Simona
S
Vigário
Ana M
AM
Silva
Susana
S
Leirião
Patricia
P
Carapau
Daniel
D
Armas-Portela
Rosario
R
Comoglio
Paolo M
PM
Rodriguez
Ana
A
Mota
Maria M
MM
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
D000199:Actins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met