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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.
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“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]
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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
Gringhuis, S. I., Kaptein, T. M., Wevers, B. A., Theelen, B., van der Vlist, M., Boekhout, T., & Geijtenbeek, T. B. H. (2012) · Nature Immunology · doi:10.1038/ni.2222 · Cited by 627
Hise, A. G., Tomalka, J. A., Ganesan, S., Patel, K., Hall, B. A., Brown, G. D., & Fitzgerald, K. A. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.05.002 · Cited by 582
Elements of the Yeast Pheromone Response Pathway Required for Filamentous Growth of Diploids
Liu, H., Styles, C. A., & Fink, G. R. (1993) · Science · doi:10.1126/science.8259520 · Cited by 500
Emerging inflammasome effector mechanisms
Lamkanfi, M. (2011) · Nature reviews. Immunology · doi:10.1038/nri2936 · Cited by 448
A Phenotypic Profile of the Candida albicans Regulatory Network
Homann, O. R., Dea, J., Noble, S. M., & Johnson, A. D. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000783 · Cited by 444 · cited 2×
“from the Fungal Genetics Stock Center (21).”
Saccharomyces cerevisiae S288C Has a Mutation in FL08, a Gene Required for Filamentous Growth
Liu, H., Styles, C. A., & Fink, G. R. (1996) · Genetics · doi:10.1093/genetics/144.3.967 · Cited by 382
Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis
Lara-Tejero, M., Sutterwala, F. S., Ogura, Y., Grant, E. P., Bertin, J., Coyle, A. J., Flavell, R. A., & Galán, J. E. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060206 · Cited by 371
Self-citationDeficiency in caspase-9 or caspase-3 induces compensatory caspase activation
Zheng, T. S., Hunot, S., Kuida, K., Momoi, T., Srinivasan, A. N., Nicholson, D. W., Lazebnik, Y. A., & Flavell, R. A. (2000) · Nature Medicine · doi:10.1038/81343 · Cited by 309
Dynamic, Morphotype-Specific Candida albicans β-Glucan Exposure during Infection and Drug Treatment
Wheeler, R. T., Kombe, D., Agarwala, S. D., & Fink, G. R. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000227 · Cited by 309
Organ-Specific Innate Immune Responses in a Mouse Model of Invasive Candidiasis
Lionakis, M. S., Lim, J. K., Lee, C.-C. R., & Murphy, P. M. (2011) · Journal of Innate Immunity · doi:10.1159/000321157 · Cited by 302
Cutting Edge: Candida albicans Hyphae Formation Triggers Activation of the Nlrp3 Inflammasome
Joly, S., Ma, N., Sadler, J. J., Soll, D. R., Cassel, S. L., & Sutterwala, F. S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901323 · Cited by 296
Self-citationBergsbaken, T., & Cookson, B. T. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030161 · Cited by 251
Snodgrass, R. G., Huang, S., Choi, I.-W., Rutledge, J. C., & Hwang, D. H. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300298 · Cited by 243
Flowers, S. A., Barker, K. S., Berkow, E. L., Toner, G., Chadwick, S. G., Gygax, S. E., Morschhäuser, J., & Rogers, P. D. (2012) · Eukaryotic Cell · doi:10.1128/ec.00215-12 · Cited by 239 · cited 2×
“albicans (37, 44); however, additional work will be required to identify the specific Upc2-regulated molecules or processes that modulate the ability of C.”
BackgroundDunkel, N., Liu, T. T., Barker, K. S., Homayouni, R., Morschhäuser, J., & Rogers, P. D. (2008) · Eukaryotic Cell · doi:10.1128/ec.00103-08 · Cited by 236
Sensing pathogens and danger signals by the inflammasome
Pedra, J. H., Cassel, S. L., & Sutterwala, F. S. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.01.006 · Cited by 233
Self-citationPortrait of Candida albicans Adherence Regulators
Finkel, J. S., Xu, W., Huang, D., Hill, E. M., Desai, J. V., Woolford, C. A., Nett, J. E., Taff, H., Norice, C. T., Andes, D. R., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002525 · Cited by 228
Global Gene Deletion Analysis Exploring Yeast Filamentous Growth
Ryan, O. W., Shapiro, R. S., Kurat, C. F., Mayhew, D. N., Baryshnikova, A., Chin, B., Lin, Z., Cox, M. J., Vizeacoumar, F. S., Cheung, D., et al. (2012) · Science · doi:10.1126/science.1224339 · Cited by 216
Tomalka, J. A., Ganesan, S., Azodi, E., Patel, K., Majmudar, P. R., Hall, B. A., Fitzgerald, K. A., & Hise, A. G. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002379 · Cited by 188
Cormack, B. P., & Falkow, S. (1999) · Genetics · doi:10.1093/genetics/151.3.979 · Cited by 180
The Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence
Youm, Y.-H., Kanneganti, T.-D., Vandanmagsar, B., Zhu, X., Ravussin, A., Adijiang, A., Owen, J. S., Thomas, M. J., Francis, J., Parks, J. S., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2011.11.005 · Cited by 172
Bliss, J. M., Basavegowda, K. P., Watson, W. J., Sheikh, A. U., & Ryan, R. M. (2008) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e31815bb69d · Cited by 154
Inflammatory Monocytes Mediate Early and Organ-Specific Innate Defense During Systemic Candidiasis
Ngo, L. Y., Kasahara, S., Kumasaka, D. K., Knoblaugh, S. E., Jhingran, A., & Hohl, T. M. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit413 · Cited by 135
Silent chromatin determines target preference of the Saccharomyces retrotransposon Ty5
Zou, S., & Voytas, D. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7412 · Cited by 128
Znaidi, S., Weber, S., Zin Al-Abdin, O., Bomme, P., Saidane, S., Drouin, S., Lemieux, S., De Deken, X., Robert, F., & Raymond, M. (2008) · Eukaryotic Cell · doi:10.1128/ec.00070-08 · Cited by 119
Thriving within the host: Candida spp. interactions with phagocytic cells
Miramón, P., Kasper, L., & Hube, B. (2013) · Medical Microbiology and Immunology · doi:10.1007/s00430-013-0288-z · Cited by 113
Fungal Immune Evasion in a Model Host–Pathogen Interaction: Candida albicans Versus Macrophages
Jiménez-López, C., & Lorenz, M. C. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003741 · Cited by 96
Live Candida albicans Suppresses Production of Reactive Oxygen Species in Phagocytes
Wellington, M. A., Dolan, K., & Krysan, D. J. (2008) · Infection and Immunity · doi:10.1128/iai.00860-08 · Cited by 89
Self-citationLohberger, A., Coste, A. T., & Sanglard, D. (2013) · Eukaryotic Cell · doi:10.1128/ec.00245-13 · Cited by 83
van de Veerdonk, F. L., Joosten, L. A. B., Devesa, I., Mora-Montes, H. M., Kanneganti, T., Dinarello, C. A., van der Meer, J. W. M., Gow, N. A. R., Kullberg, B. J., & Netea, M. G. (2009) · The Journal of Infectious Diseases · doi:10.1086/597274 · Cited by 77
Candida albicans Morphogenesis Is Not Required for Macrophage Interleukin 1β Production
Wellington, M. A., Koselny, K., & Krysan, D. J. (2012) · mBio · doi:10.1128/mbio.00433-12 · Cited by 67
Self-citationCaspase-1 activity is required to bypass macrophage apoptosis upon Salmonella infection
Puri, A. W., Brož, P., Shen, A., Monack, D. M., & Bogyo, M. S. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1023 · Cited by 66
Joly, S., Eisenbarth, S. C., Olivier, A. K., Williams, A., Kaplan, D. H., Cassel, S. L., Flavell, R. A., & Sutterwala, F. S. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201715 · Cited by 65
Self-citationGarcía‐Rodas, R., González‐Camacho, F., Rodrı́guez-Tudela, J. L., Cuenca‐Estrella, M., & Zaragoza, Ó. (2011) · Infection and Immunity · doi:10.1128/iai.00044-11 · Cited by 56
Naip5/Birc1e and susceptibility to Legionella pneumophila
Fortier, A. H., Diez, E., & Gros, P. (2005) · Trends in Microbiology · doi:10.1016/j.tim.2005.05.007 · Cited by 55
Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice
Tuite, A. R., Elias, M., Picard, S., Mullick, A., & Gros, P. (2005) · Genes and Immunity · doi:10.1038/sj.gene.6364254 · Cited by 54
An Introduction to the Medically Important Candida Species
Moran, G. P., Coleman, D. C., & Sullivan, D. J. (2014) · ASM Press eBooks · doi:10.1128/9781555817176.ch2 · Cited by 51
Antimicrobial functions of inflammasomes
Chen, K. W., & Schroder, K. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.02.004 · Cited by 39
Vázquez, J. A., & Sobel, J. D. (2003) · doi:10.1093/oso/9780195148091.003.0011 · Cited by 18
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d’Enfert, C., Kaune, A.-K., Alaban, L. R., Chakraborty, S., Cole, N. L., Delavy, M., Kosmala, D., Marsaux, B., Fróis-Martins, R., Morelli, M., et al. (2020) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaa060 · Cited by 367
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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
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