Hepatocyte growth factor and its receptor are required for malaria infection

Margarida Carrolo, Silvia Giordano, Laura Cabrita-Santos, Simona Corso, Ana M. Vigário, Susana Silva, Patricia Leirião, Daniel Carapau, Rosario Armas-Portela, Paolo M. Comoglio, Ana Rodriguez, Maria M. Mota

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1363-1369
Number of pages7
JournalNature Medicine
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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