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.

journal_name

Elife

journal_title

eLife

authors

Lissner MM,Cumnock K,Davis NM,Vilches-Moure JG,Basak P,Navarrete DJ,Allen JA,Schneider D

doi

10.7554/eLife.60165

subject

Has Abstract

pub_date

2020-10-06 00:00:00

issn

2050-084X

pii

60165

journal_volume

9

pub_type

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