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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.

SUBMITTER: Lissner MM

PROVIDER: S-EPMC7538157 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Lissner Michelle M MM Cumnock Katherine K Davis Nicole M NM Vilches-Moure José G JG Basak Priyanka P Navarrete Daniel J DJ Allen Jessica A JA Schneider David D

eLife 20201006

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 <i>Ahr<sup>-/-</sup ...[more]

PMID: 33021470

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