Candida auris uses metabolic strategies to escape and kill macrophages while avoiding robust activation of the NLRP3 inflammasome response
Open accessAbstract
Metabolic adaptations regulate the response of macrophages to infection. The contributions of metabolism to macrophage interactions with the emerging fungal pathogen Candida auris are poorly understood. Here, we show that C. auris-infected macrophages undergo immunometabolic reprogramming and increase glycolysis but fail to activate a strong interleukin (IL)-1β cytokine response or curb C. auris growth. Further analysis shows that C. auris relies on its own metabolic capacity to escape from macrophages and proliferate in vivo. Furthermore, C. auris kills macrophages by triggering host metabolic stress through glucose starvation. However, despite causing macrophage cell death, C. auris does not trigger robust activation of the NLRP3 inflammasome. Consequently, inflammasome-dependent responses remain low throughout infection. Collectively, our findings show that C. auris uses metabolic regulation to eliminate macrophages while remaining immunologically silent to ensure its own survival. Thus, our data suggest that host and pathogen metabolism could represent therapeutic targets for C. auris infections.
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During Staphylococcus aureus skin infection, dermal fibroblasts differentiate into adipocytes and produce AMP, mainly CAMP, for host defense.
“During Staphylococcus aureus skin infection, the dermal fibroblasts differentiate into adipocytes and produce AMP, mainly CAMP, for host defense [43]”
C. auris replicates within macrophages by bypassing the NLRP3 pathway.
“Recent evidence suggests that C. auris replicates within macrophages by bypassing the NLRP3 pathway (33, 34).”
From Cell aggregation mediated by <i>ACE2</i> deletion in <i>Candida auris</i> modulates fungal colonization and host immune responses in the skin (2024) · cites this paper as [34]
C. auris can replicate within macrophages, using metabolic plasticity to survive and escape the phagolysosomal environment.
“Recent studies showed that C. auris can replicate within macrophages, using metabolic plasticity to survive and escape the phagolysosomal environment [90,91].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [90]
C. auris induces host glucose starvation and metabolic stress, leading to macrophage death without triggering classical activation of the NLRP3 inflammasome or its effector molecules IL-1β and caspase-1, unlike C. albicans.
“The fungus induces host glucose starvation and metabolic stress, leading to macrophage death without triggering classical activation of the NLRP3 inflammasome or its effector molecules IL-1β and caspase-1, unlike C. albicans [90].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [90]
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Innate immune responses against the fungal pathogen Candida auris
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Mechanisms of pathogenicity for the emerging fungus Candida auris
Horton, M. V., Holt, A. M., & Nett, J. E. (2023) · PLOS Pathogens · doi:10.1371/journal.ppat.1011843 · Cited by 67 · see citing works
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Balakumar, A., Cox, A., & Thangamani, S. (2024) · mSphere · doi:10.1128/msphere.00734-24 · Cited by 12 · see citing works
Host–Candida auris interactions in the skin
Thangamani, S., Balakumar, A., Datta, A., Bryak, G., & Lionakis, M. S. (2026) · PLOS Pathogens · doi:10.1371/journal.ppat.1014075 · Cited by 3 · see citing works
- Authors
- Weerasinghe, H., Simm, C., Djajawi, T. M., Tedja, I., Lo, T. L., Simpson, D. S., Shasha, D., Mizrahi, N., Olivier, F. A. B., Speir, M., Lawlor, K. E., Ben-Ami, R., & Traven, A.
- Affiliations
- Monash University (AU)
- Hudson Institute of Medical Research (AU)
- The University of Melbourne (AU)
- Tel Aviv University (IL)
- Tel Aviv Sourasky Medical Center (IL)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Corresponding author
- Traven, Ana
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2023-05
- Volume
- 42
- Issue
- 5
- Pages
- 112522
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W4377046861
- Cited by
- 47
- References
- 10
- Citations by year
- 2026: 17 · 2025: 10 · 2024: 15 · 2023: 5
- FWCI
- 9.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Australian Research Council
- National Health and Medical Research Council
- Ministry of Science and Technology (88555)
- Monash University
- Israel Science Foundation (442/18)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida auris, macrophages, immunometabolic reprogramming, glycolysis, NLRP3 inflammasome, IL-1β, glucose deprivation, fungal pathogen survival
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Candida auris, Candida albicans, Macrophages, Interleukin-1beta, Inflammasomes
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