TY - JOUR
T1 - Hepatocyte growth factor and its receptor are required for malaria infection
AU - Carrolo, Margarida
AU - Giordano, Silvia
AU - Cabrita-Santos, Laura
AU - Corso, Simona
AU - Vigário, Ana M.
AU - Silva, Susana
AU - Leirião, Patricia
AU - Carapau, Daniel
AU - Armas-Portela, Rosario
AU - Comoglio, Paolo M.
AU - Rodriguez, Ana
AU - Mota, Maria M.
PY - 2003/11
Y1 - 2003/11
N2 - 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.
AB - 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.
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U2 - 10.1038/nm947
DO - 10.1038/nm947
M3 - Article
C2 - 14556002
AN - SCOPUS:0345708275
VL - 9
SP - 1363
EP - 1369
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 11
ER -