Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection.
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...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-11-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011719&type=printable |
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| _version_ | 1849468470923624448 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Grace P Carreno-Florez |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bc271073a1df4e65b1bf723cc4ded213 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2023-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-bc271073a1df4e65b1bf723cc4ded2132025-08-20T03:25:50ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-11-011911e101171910.1371/journal.ppat.1011719Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection.Grace P Carreno-FlorezBrian R KocakMatthew R HendricksJeffrey A MelvinKatrina B MarJessica KosanovichRachel L CumberlandGreg M DelgoffeSruti ShivaKerry M EmpeyJohn W SchogginsJennifer M BombergerClinical 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011719&type=printable |
| spellingShingle | 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 Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection. PLoS Pathogens |
| title | Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection. |
| title_full | Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection. |
| title_fullStr | Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection. |
| title_full_unstemmed | Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection. |
| title_short | Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection. |
| title_sort | interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011719&type=printable |
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