Cited by 64Antifungal resistance and susceptibilityIron Metabolism and Disordersinterferon and immune responses

Type I Interferon Response Dysregulates Host Iron Homeostasis and Enhances Candida glabrata Infection

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Riedelberger, Michael, Penninger, Philipp, Tscherner, Michael, Seifert, Markus, Jenull, Sabrina, Brunnhofer, Carina, Scheidl, Bernhard, Tsymala, Irina +7 more·2020·Cell Host & Microbe

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 promote the dysregulation of iron homeostasis in macrophages during systemic infections with the intracellular pathogen Candida glabrata, leading to fungal survival and persistence. By engaging JAK1, IFNs-I disturb the balance of the transcriptional activator NRF2 and repressor BACH1 to induce downregulation of the key iron exporter Fpn1 in macrophages. 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, facilitating fungal intracellular replication and immune evasion. Thus, IFNs-I are central regulators of iron homeostasis, which can impact infection, and restricting iron bioavailability may offer therapeutic strategies to combat invasive fungal infections.

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Crossref · 10.1016/j.chom.2020.01.023

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Authors
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.
Affiliations
  • Max Perutz Labs (AT)
  • Innsbruck Medical University (AT)
  • TU Wien (AT)
  • University of Veterinary Medicine Vienna (AT)
Corresponding author
Kuchler, Karl
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2020-03
Volume
27
Issue
3
Pages
454-466.e8
ISSN
1931-3128 (ISSN-L)
OpenAlex
W3006691620
Cited by
64
References
107
Citations by year
2026: 4 · 2025: 9 · 2024: 12 · 2023: 9 · 2022: 7 · 2021: 16 · 2020: 7
FWCI
1.28
Type
journal article
Language
en
Open access
Locations
  • Cell Host & Microbe (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Seventh Framework Programme
  • Austrian Science Fund
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
type I interferon, iron homeostasis, Candida glabrata, macrophages, Nrf2, BACH1, immune evasion, invasive fungal infections
MeSH terms
Ferroportin, Adult, Animals, Candidiasis, Cells, Cultured, Female, Homeostasis, Humans, Interferon Type I, Iron, Macrophages, Male, Mice, Inbred C57BL, Phagosomes, Spleen, Mice, Knockout, Cation Transport Proteins, Candida glabrata, Basic-Leucine Zipper Transcription Factors, NF-E2-Related Factor 2, Janus Kinase 1, Immune Evasion

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