Metabolic profiling during malaria reveals the role of the aryl hydrocarbon receptor in regulating kidney injury
Abstract
Systemic metabolic reprogramming induced by infection exerts profound, pathogen-specific effects on infection outcome. Here, we detail the host immune and metabolic response during sickness and recovery in a mouse model of malaria. We describe extensive alterations in metabolism during acute infection, and identify increases in host-derived metabolites that signal through the aryl hydrocarbon receptor (AHR), a transcription factor with immunomodulatory functions. We find that Ahr-/- mice are more susceptible to malaria and develop high plasma heme and acute kidney injury. This phenotype is dependent on AHR in Tek-expressing radioresistant cells. Our findings identify a role for AHR in limiting tissue damage during malaria. Furthermore, this work demonstrates the critical role of host metabolism in surviving infection.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 06, 2020
- Source ID
- 10.7554/elife.60165
Entities
People
- Daniel J. Navarrete
- David Schneider
- Jessica A Allen
- José G Vilches-moure
- Katherine Cumnock
- Michelle M Lissner
- Nicole M. Davis
- Priyanka Basak
Organizations
- Columbia College
- Defense Advanced Research Projects Agency
- National Institutes of Health
- National Science Foundation
- Stanford University