Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection

Grace P. Carreno-Florez, Brian R. Kocak, Matthew R. Hendricks, Jeffrey A. Melvin, Katrina B. Mar, Jessica Kosanovich, Rachel L. Cumberland, Greg M. Delgoffe, Sruti Shiva, Kerry M. Empey, John W. Schoggins, Jennifer M. Bomberger

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Clinical studies report that viral infections promote acute or chronic bacterial infections at multiple host sites. These viral-bacterial co-infections are widely linked to more severe clinical outcomes. In experimental models in vitro and in vivo, virus-induced interferon responses can augment host susceptibility to secondary bacterial infection. Here, we used a cell-based screen to assess 389 interferon-stimulated genes (ISGs) for their ability to induce chronic Pseudomonas aeruginosa infection. We identified and validated five ISGs that were sufficient to promote bacterial infection. Furthermore, we dissected the mechanism of action of hexokinase 2 (HK2), a gene involved in the induction of aerobic glycolysis, commonly known as the Warburg effect. We report that HK2 upregulation mediates the induction of Warburg effect and secretion of L-lactate, which enhances chronic P. aeruginosa infection. These findings elucidate how the antiviral immune response renders the host susceptible to secondary bacterial infection, revealing potential strategies for viral-bacterial co-infection treatment.

Original languageEnglish (US)
Article numbere1011719
JournalPLoS pathogens
Volume19
Issue number11 November
DOIs
StatePublished - Nov 2023

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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