EMBO Fellows Meeting 2012

Vanessa Luis
EMBO Fellows Meeting 2012
Lipid metabolism and malaria liver infection
Abstract
The liver stage constitutes the first obligatory step of Plasmodium infection in the vertebrate host, being
hepatocytes the only cell type that can efficiently support complete growth and development of the
Plasmodium exoerythrocytic form (EEF). This unique cellular environment allows the replication of single
sporozoites into thousands of new merozoites over a period, for rodent infections, as short as two days.
This extensive proliferation rate necessarily requires the availability of sufficient lipids for the synthesis of large
amounts of additional membranes. Interestingly, while Plasmodium lacks some key enzymes for lipid
synthesis, hepatocytes are specialized in the biosynthesis of lipids and the liver is known to play a central role
in lipid homeostasis. It is therefore tempting to hypothesize that hepatocytes are favoured by Plasmodium
sporozoites because of their inherent ability to mobilize lipids. In fact, ongoing work in the lab shows that by
engaging the host cell’s resources to its own benefit (thereby fulfilling its molecular needs for multiplication),
Plasmodium development inside the hepatocyte leads to alterations in host cell lipid metabolism. On the other
hand, although only recently appreciated, there is an overwhelming amount of evidence that the metabolic
systems, namely lipid metabolism, are integrated with pathogen-sensing and immune responses. Here, we
observe that the modulation of host lipid metabolism through the administration of a rich-fat diet almost
completely abrogates Plasmodium liver infection. We now propose to explain the mechanism behind the
observed effect of the administration of exogenous lipids on infection by interrogating both the activation of
the immune system and the metabolic alterations.
Instituto de Medicina Molecular, Lisboa, Portugal
14-17 June 2012, Heidelberg, Germany