CGIDR Stories

Publication Q&A: Liver Stage Malaria Infection is Controlled by Host Regulators of Lipid Peroxidation

May 2019 – Dr. Alexis Kaushansky shares insights from a recent publication in Cell Death & Differentiation with contributing authors from Kaushansky and Aderem labs at the Center for Global Infectious Disease Research (CGIDR).

Liver Stage Malaria Infection is Controlled by Host Regulators of Lipid Peroxidation

Heather S. Kain, Elizabeth K. K. Glennon, Kamalakannan Vijayan, Nadia Arang, Alyse N. Douglass, Chelsea L. Fortin, Meghan Zuck, Adam J. Lewis, Samantha L. Whiteside, Denali R. Dudgeon, Jarrod S. Johnson, Alan Aderem, Kelly R. Stevens & Alexis Kaushansky

Published in Cell Death & Differentiation, May 2019

Read article in Cell Death & Differentiation

What were your key findings?

One of the interests of our lab is how the malaria parasite is regulated in the liver. Infection of the liver is an essential early stage of malaria that happens before disease symptoms are visible. We know that our immune system responds to this early stage of infection. Yet some parasites persist and establish themselves, causing disease or death. If we could boost our natural ability to fight the malaria parasite while it is in the liver, we could prevent the symptoms of disease.

We recently identified a role for a signaling pathway in the liver that regulates malaria infection. This signaling pathway uses reactive forms of oxygen to control fat usage in cells. We manipulated the pathway with drugs or genetic tricks to study its effect on malaria. Blocking this pathway impaired parasite growth while stimulating this pathway enhanced growth. We are hopeful that our findings will guide new tools and therapies to stop malaria parasites in the liver, before they cause disease.

What are the broad implications of this research?

Our research shows how the malaria parasite uses a non-canonical immune signaling pathway in the liver. This finding was unexpected, and it broadens our understanding of how liver cells respond to infection. The genes in the pathway are potential therapeutic targets for drug and vaccine development. How other infectious diseases might use this pathway is not known, but a promising area for future research. If this pathway has a role in other infections we might be able to manipulate it and boost our body's ability to fight many infections at once.

Why do we need to develop better ways to treat, prevent and diagnose malaria?

Malaria is a major global health concern with severe risk of death in children under the age of five. While people living in areas with malaria develop some immunity, pregnant women remain at risk. Our best strategy for controlling malaria is to try reduce exposure, for example, sleeping with a bed net. Yet this is impractical and cannot alone eradicate the disease.

Over the past few years, deaths from malaria have remained steady and drug resistance is on the rise. Moreover, changes in climate threatens to spread the risk of disease to new groups of people. The regions where we find mosquitoes that spread malaria is increasing. Thus, we need new strategies and approaches to eliminate malaria.

Seattle Children’s CGIDR contributing authors:

  • Alan Aderem, professor
  • Elizabeth Glennon, fellow, Kaushansky Lab
  • Alexis Kaushansky, associate professor
  • Samantha Whiteside, research scientist, Kaushansky Lab
  • Kamalakannan Vijayan, fellow, Kaushansky Lab