Metabolic profiling during malaria reveals the role of the aryl hydrocarbon receptor in regulating kidney injury

Elife. 2020 Oct 6:9:e60165. doi: 10.7554/eLife.60165.


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.

Keywords: aryl hydrocarbon receptor; infectious disease; malaria; metabolism; microbiology; mouse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / parasitology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Female
  • Malaria, Falciparum / complications
  • Malaria, Falciparum / metabolism*
  • Male
  • Metabolome
  • Mice
  • Mice, Inbred C57BL
  • Plasmodium falciparum / physiology
  • Receptors, Aryl Hydrocarbon / genetics*
  • Receptors, Aryl Hydrocarbon / metabolism


  • Ahr protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Receptors, Aryl Hydrocarbon

Associated data

  • GEO/GSE150268