The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Candida albicans Triggers NLRP3-Mediated Pyroptosis in Macrophages
Open accessAbstract
Pyroptosis is an inflammasome-mediated programmed cell death pathway triggered in macrophages by a variety of stimuli, including intracellular bacterial pathogens. Activation of pyroptosis leads to the secretion of interleukin-1β (IL-1β) and pore-mediated cell lysis. Although not considered an intracellular pathogen, Candida albicans is able to kill and, thereby, escape from macrophages. Here, we show that C. albicans-infected bone marrow-derived macrophages (BMDM) and murine J774 macrophages undergo pyroptotic cell death that is suppressed by glycine and pharmacologic inhibition of caspase-1. Infection of BMDM harvested from mice lacking components of the inflammasome revealed that pyroptosis was dependent on caspase-1, ASC, and NLRP3 and independent of NLRC4. In contrast to its role during intracellular bacterial infection, pyroptosis does not restrict C. albicans replication. Nonfilamentous Candida spp. did not trigger pyroptosis, while Candida krusei, which forms pseudohyphae in macrophages, triggered much lower levels than did C. albicans. Interestingly, a Saccharomyces cerevisiae strain from the filamentous background Σ1278 also triggered low, but significant, levels of pyroptosis. We have found that deletion of the transcription factor UPC2 decreases pyroptosis but has little effect on filamentation in the macrophage. In addition, a gain-of-function mutant of UPC2 induces higher levels of pyroptosis than does a matched control strain. Taken together, these data are most consistent with a model in which filamentation is necessary but not sufficient to trigger NLRP3 inflammasome-mediated pyroptosis. This is the first example of a fungal pathogen triggering pyroptosis and indicates that C. albicans-mediated macrophage damage is not solely due to hypha-induced physical disruption of cellular integrity.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Among the known C. albicans virulence factors20, filamentation21 plays a key role in phagocytosis escape mediated through physical processes or by triggering NLRP3/caspase-1 inflammasome-dependent lysis22,23.”
From The δ subunit of F1Fo-ATP synthase is required for pathogenicity of Candida albicans (2021) · cites this paper as [23]
Citations
Cites
Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475
Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
Miao, E. A., Leaf, I. A., Treuting, P. M., Mao, D. P., Dors, M., Sarkar, A., Warren, S. E., Wewers, M. D., & Aderem, A. (2010) · Nature Immunology · doi:10.1038/ni.1960 · Cited by 1,336
Caspase‐1‐induced pyroptotic cell death
Miao, E. A., Rajan, J. V., & Aderem, A. A. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01044.x · Cited by 1,162
Fink, S. L., & Cookson, B. T. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00751.x · Cited by 1,114
Sensing and reacting to microbes through the inflammasomes
Franchi, L., Muñoz-Planillo, R., & Núñez, G. (2012) · Nature Immunology · doi:10.1038/ni.2231 · Cited by 1,046
Sutterwala, F. S., Ogura, Y., Szczepanik, M., Lara-Tejero, M., Lichtenberger, G. S., Grant, E. P., Bertin, J., Coyle, A. J., Galán, J. E., Askenase, P. W., et al. (2006) · Immunity · doi:10.1016/j.immuni.2006.02.004 · Cited by 980
Self-citationSyk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence
Groß, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschläger, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V. L. J., et al. (2009) · Nature · doi:10.1038/nature07965 · Cited by 946
Calderone, R. (2012) · ASM Press eBooks · Cited by 912
Candida albicans morphogenesis and host defence: discriminating invasion from colonization
Gow, N. A. R., van de Veerdonk, F. L., Brown, A. J. P., & Netea, M. G. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2711 · Cited by 888
Noble, S. M., French, S., Kohn, L. A., Chen, V., & Johnson, A. D. (2010) · Nature Genetics · doi:10.1038/ng.605 · Cited by 678
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–227 of 227
Hall, R. A. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734004638.793579588
Yi, X., Wang, Y., Zhang, J., Huang, S., & Liu, M. (2022) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2021-0738
Interactions Between Intracellular Fungal Pathogens and Host Phagocytes
Case, N. T., Robbins, N., & Cowen, L. E. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00042-0
Hall, R. A. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735513165.793575579
Gow, N. A. R., & Yadav, B. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733159930.793545575
Hube, B., & Gresnigt, M. S. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.738437887.793577404
McFadden, M. J., Reynolds, M. B., Michmerhuizen, B. C., Olafsson, E. B., Anderson, F. M., Schultz, T. L., O’Riordan, M. X., & O’Meara, T. R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.02.560560
IL-18 production is required for the generation of a Th1 response during chromoblastomycosisPreprint
Ferreira, L. G., & Almeida (2024) · Research Square · doi:10.21203/rs.3.rs-4163904/v1
Infection Models for Human Pathogenic Fungi
Jacobsen, I. D. (2024) · The mycota · doi:10.1007/978-3-031-64853-3_9
Management of Denture Stomatitis with a Herbal Armamentarium
Chauhan, V., Saxena, P., Nautiyal, A., & Gupta, P. (2024) · Current Dentistry · doi:10.2174/012542579x317149241202064449
Promising Role of Fruitless Wolfberry Bud Tea in Combating Nakaseomyces glabratus Resistance
Zhang, L., Ma, Z., Zhou, X., Zhang, Z., & Wu, T. (2025) · Pathogens · doi:10.3390/pathogens14040351
The Oral Mucosa-Fungi Interactome
Neelakantan, P., Kalimuthu, S., Pudipeddi, A., Krom, B. P., Ramage, G., Butcher, M. C., & Brown, J. L. (2025) · Springer series on biofilms · doi:10.1007/978-3-031-82202-5_7
Zou, Y., Bai, S., Han, M., Yang, X., Cheng, X., Wu, J., Xia, Z., & Yang, R. (2025) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2025.104021
Yue, H., Liu, S., Bai, Y., Zhu, W., Tian, J., Xu, X., & Liu, Q. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s551135
Bezrodny, S. L. (2026) · Medical alphabet · doi:10.33667/2078-5631-2025-34-7-14
Chen, J., Zhou, B., Zou, J., Wang, P., Meng, X., Huang, P., Chen, J., & Cao, H. (2026) · Microbial Pathogenesis · doi:10.1016/j.micpath.2026.108377
Fungal hyphae instigate non-canonical inflammatory cell death in macrophagesPreprint
Dietschmann, A., Musiejovsky, L., Krüger, T., Bohaen, C. K., Dinçer, S., Bruggeman, F., Oktay, C., Valentine, M., Himmel, M., Wirtz, S., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-8296333/v1
Charlet, R. (2022) · theses.fr (ABES) · doi:10.70675/11b08f90z8d0dz43efz96ffzf2527c076034
Cell membrane-derived nanotherapeutic for combating Candida albicans infections
Zhou, Z., Feng, K., Sun, L., Zhang, J. A., Shen, W., Barua, S., Griffiths, A., Gao, W., & Zhang, L. (2026) · Cell Biomaterials · doi:10.1016/j.celbio.2026.100487
Yau, K. P. S., Erlich, J. R., Rodriguez, P., McArdle, S., Nowell, C. J., Tate, M., Onyuru, J., Ratnavel, A., Desai, A., Symington, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-75022-8
Chen, Y., Qu, Z., Xie, Z., Wang, X., Tong, Z., Yang, L., Zhang, X., Chen, L., & Dong, B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1843553
Molnár, A., Vaz, A. G., Homa, M., Tyagi, C., Bodai, L., Nagy, G., Zsindely, N., Németh, D., Sinka, R., Kedves, A., et al. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1904531
From confrontation to co-adaptation: the dynamic dialogue of Candida albicans and macrophages
Miramón, P., Wilson, H. B., & Lorenz, M. C. (2026) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00191-22
Soni, A., Vrzoňová, R., Paulovičová, L., Bzducha‐Wróbel, A., & Farkaš, P. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.154672
Fungal Phosphatase-Dependent Induction of Host Cell Pyroptosis by Candidalysin
Hong, Y.-M., Wang, X., Wang, L., Xiong, S.-C., Zhou, J., Zhang, T.-Y., Sun, Y.-Y., Wu, D., Mao, Y., Ma, Y.-J., et al. (2026) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.6c00688
Limin, F., Huang, R., Wang, K., Ni, M., Nong, X., Xie, Z., Fu, B., Mo, L., Lan, Y., Xu, Q., et al. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1960578
Metadata
- Authors
- Wellington, M., Koselny, K., Sutterwala, F. S., & Krysan, D. J.
- Affiliations
- University of Rochester Medicine (US)
- University of Iowa (US)
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2014-02
- Volume
- 13
- Issue
- 2
- Pages
- 329-340
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC3910967
- OpenAlex
- W2117231363
- Cited by
- 227
- References
- 49
- Citations by year
- 2026: 16 · 2025: 10 · 2024: 9 · 2023: 18 · 2022: 18 · 2021: 22 · 2020: 25 · 2019: 19 · 2018: 26 · 2017: 19 · 2016: 16 · 2015: 19 · 2014: 10
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Center, University of Rochester
- National Institute of Allergy and Infectious Diseases (R01AI087630, R01AI098450)
- National Institute of Environmental Health Sciences (P30ES005605)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Candida albicans, pyroptosis, NLRP3 inflammasome, macrophages, caspase-1, ASC, NLRC4, fungal pathogens, filamentation, pseudohyphae, Candida krusei, Saccharomyces cerevisiae, UPC2, IL-1β, bone marrow-derived macrophages, programmed cell death
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Candida albicans, Carrier Proteins, Cells, Cultured, DNA Replication, Fungal Proteins, Glycine, Macrophages, Mice, Inbred BALB C, Mice, Inbred C57BL, Trans-Activators, Cell Death, Caspase 1, Mice, Inflammasomes, Caspase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
