Riedelberger, M., Penninger, P., Tscherner, M., Seifert, M., Jenull, S., Brunnhofer, C., Scheidl, B., Tsymala, I., Bourgeois, C., Petryshyn, A., Glaser, W., Limbeck, A., Strobl, B., Weiss, G., & Kuchler, K. (2020). Type I Interferon Response Dysregulates Host Iron Homeostasis and Enhances Candida glabrata Infection. Cell Host & Microbe, 27(3), 454-466.e8. https://doi.org/10.1016/j.chom.2020.01.023
E164-01-2 - Forschungsgruppe Oberflächen-, Spurenanalytik und Chemometrie
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Journal:
Cell Host & Microbe
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ISSN:
1931-3128
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Date (published):
2020
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Number of Pages:
13
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Peer reviewed:
Yes
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Keywords:
Microbiology; Virology; Parasitology
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Abstract:
Type I interferons (IFNs-I) fulfil multiple protective functions during pathogenic infections, but they can also cause detrimental effects and enhance immunopathology. Here, we report that IFNs-I pro-mote the dysregulation of iron homeostasis in mac-rophages during systemic infections with the intra-cellular pathogen Candida glabrata, leading to fungal survival and persistence. By engaging JAK1, IFNs-I disturb the balance of the transcriptional acti-vator NRF2 and repressor BACH1 to induce downre-gulation of the key iron exporter Fpn1 in macro-phages. This leads to enhanced iron accumulation in the phagolysosome and failure to restrict fungal access to iron pools. As a result, C. glabrata acquires iron via the Sit1/Ftr1 iron transporter system, facili-tating fungal intracellular replication and immune evasion. Thus, IFNs-I are central regulators of iron homeostasis, which can impact infection, and re-stricting iron bioavailability may offer therapeutic strategies to combat invasive fungal infections.