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Chronic Mucocutaneous Candidiasis in Humans with Inborn Errors of Interleukin-17 Immunity
Open accessAbstract
Chronic yeast infections in the absence of other infections result from genetic deficiencies in proinflammatory host responses.
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In the citing paper
“IL-17-mediated immunity is central to mucocutaneous host defense against fungi such as C. albicans and Malassezia [10,99,100].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [99]
Experimental — accuracy not yet measuredIn the citing paper
“analysis of Th17 cells in different tissue sites has revealed that Th17 cells may exhibit distinct transcriptional profiles associated with either homeostatic or pathogenic functions”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [43]
In the citing paper
“intestinal non-pathogenic/homeostatic Th17 cells specific for segmented filamentous bacteria (SFB) have a transcriptome that differs markedly from the pro-inflammatory Th17 cells elicited by Helicobacter hepaticus (H. hepaticus) in mice defective for induced intestinal Treg cells”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [43]
In the citing paper
“In the Il10−/− model of colitis, in which IL-10-deficient mice develop spontaneous microbiota-dependent colitis, Th17 cells were identified as the main immune population mediating the inflammatory immune response [43, 133].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [43]
In the citing paper
“In Helicobacter hepaticus- dependent colitis, pathobiont-specific inflammatory Th17 cells are major mediators of intestinal inflammation [43].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [43]
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Cites
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Prevalence of Candida species in Psoriasis
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“For example, IL-17 production by γδ T cells (γδT17) was shown to be important for effective bacterial clearance [31–41] or control of fungal burden [42, 43].”
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“litis (18, 19), arthritis (20), and fungal (21, 22) and bacterial infections (23, 24).”
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The IL ‐23/ T h17 axis is involved in the adaptive immune response to B acillus anthracis in humans
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The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans
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“In a subgroup of PIDs, predisposition to superficial candidiasis may be the only or the dominant characteristic of the underlying genetic disorder (CMC disease, CMCD) [9].”
BackgroundInfluentialTriple Cytokine FluoroSpot Analysis of Human Antigen-Specific IFN-γ, IL-17A and IL-22 Responses
Dillenbeck, T., Gelius, E., Fohlstedt, J., & Ahlborg, N. (2014) · Cells · doi:10.3390/cells3041116 · Cited by 17
“Th17 cells are involved in immunity against extracellular pathogens including Candida albicans and Staphylococcus aureus [5,6] and Th22 cells, due to their expression of skin-homing receptors, appear to be recruited to the skin for tissue repair and protection against pathogens [7].”
BackgroundGrimaux, X., Leducq, S., Goupille, P., Aubourg, A., Miquelestorena‐Standley, E., & Samimi, M. (2018) · Annales de Dermatologie et de Vénéréologie · doi:10.1016/j.annder.2018.07.009 · Cited by 17
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Self-citationSwitchable Membrane Remodeling and Antifungal Defense by Metamorphic Chemokine XCL1
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“Historically, Th17 cells were identified as the key producers of IL-17A in anti-fungal protective immunity [11, 166, 173].”
BackgroundRegional specialization within the mammalian respiratory immune system
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“Consistent with these data, polymorphisms resulting in IL-17RA and IL-17F deficiency were recently identified in some patients with chronic mucocutaneous candidiasis [21].”
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“One of those markers is Signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family and an important transcription activator has been found to have an important role in invasive fungal infections (Puel et al., 2011) as it is associated to the T-helper cell 17 (Th17) pathway (Yang et…”
BackgroundRisk stratification biomarkers for Staphylococcus aureus bacteraemia
Cao, Y., Guimaraes, A., Peck, M. C., Mayba, O., Ruffin, F., Hong, K., Carrasco‐Triguero, M., Fowler, V. G., Maskarinec, S. A., & Rosenberger, C. M. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1110 · Cited by 16
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Candidiasis in patients with APS-1: low IL-17, high IFN-γ, or both?
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“a patient’s outcome in a therapy targeting another corner, or whether blocking two corners of the triangle could result in greater clinical benefits [88].”
BackgroundRecurrent Vulvovaginal Candidosis and Its Underlying Mechanisms: A Systematic Review
Lobo, M., Cerqueira, C., Rodrigues, A. G., & Lisboa, C. (2025) · Journal of Fungi · doi:10.3390/jof11050357 · Cited by 19
“Furthermore, the immune response against Candida species is compromised when IL-17 is also inhibited through genetic knockout [42].”
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“IL-17F Immune reactions in mucous membranes, including antifungal immune response [92] Combined effects with IL-17A.”
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Self-citationThe Promise of Immunogenomics at the Bedside
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“Th17 cells produce IL-17 and IL-22 that trigger β-defensin—a gene implicated in the present study—and their defects have been associated with chronic mucocutaneous candidiasis (10, 11).”
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“…of the HIES (AD-HIES) caused by mutations in STAT3, autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by antibodies directed against IL-17A/F or IL-22, and the two novel primary immune deficiencies reported in Science by Puel et al., 2011, i.e. IL-17F and IL-17 receptor alpha deficiency.”
BackgroundZhou, C., Monin, L., Gordon, R. A., Aggor, F. E. Y., Bechara, R., Edwards, T. N., Kaplan, D. H., Gingras, S., & Gaffen, S. L. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000394 · Cited by 14
“CMCD is conserved amongmany species, includingmice (16).”
BackgroundMethodInfluentialExpected impact of immunomodulatory agents during pregnancy: A newborn's perspective
Luo, Y., Acevedo, D., Baños, N., Pluma, A., Castellanos‐Moreira, R., Moreno, E., Rodríguez-García, S. C., Deyà‐Martínez, À., García‐García, A., Quesada‐Masachs, E., et al. (2023) · Pediatric Allergy and Immunology · doi:10.1111/pai.13911 · Cited by 14
Immunogenetic Profiling to Predict Risk of Invasive Fungal Diseases: Where Are We Now?
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“Furthermore, the H161R variant blocked the induction of the expression of IL8 by wild-type IL17F, acting as a natural antagonist of the cytokine (30, 31).”
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The Role of AIRE in the Immunity Against Candida Albicans in a Model of Human Macrophages
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“Patients with deficiency in IL-17RA, IL-17F, or ACT1 have defective TH17 function and CMC (11, 14, 18, 26, 37).”
BackgroundCandida gut commensalism and inflammatory disease
Gu, Z.-Q., Tseng, K.-Y., & Tsai, Y.-H. (2020) · Medicine in Microecology · doi:10.1016/j.medmic.2020.100008 · Cited by 14
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Introduction on Primary Immunodeficiency Diseases
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“Deficiencies in the IL-17 signaling, due to loss-of-function mutations in associated genes, have been linked to increased susceptibility to recurrent fungal and bacterial infections, underscoring its protective function in mucosal immunity 2 .”
Arid5a Mediates an IL-17–Dependent Pathway That Drives Autoimmunity but Not Antifungal Host Defense
Taylor, T. C., Li, Y., Li, D., Majumder, S., McGeachy, M. J., Biswas, P. S., Gingras, S., & Gaffen, S. L. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2200132 · Cited by 12
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“At barrier sites such as skin, homeostasis and absence of in fl ammation appears to depend on a tightly regulated Th17 response, since cutaneous infection is associated with Th17 de fi ciency and pathology with Th17 excess 56,57 .”
The role of IL-17 in the treatment of psoriatic arthritis
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“defects in IL-17 signaling, reinforcing the evidences of a key role cytokine in immune response against microorganisms [19].”
BackgroundTh17 cells differentiated with mycelial membranes of Candida albicans prevent oral candidiasis
Tasaki, S., Cho, T., Nagao, J.-I., Ikezaki, S., Narita, Y., Arita-Morioka, K.-I., Yasumatsu, K., Toyoda, K., Kojima, H., & Tanaka, Y. (2018) · FEMS Yeast Research · doi:10.1093/femsyr/foy018 · Cited by 12
“Moreover, deficiency of IL-17 immunity in humans also develops into oropharyngeal candidiasis (Puel et al. 2011).”
BackgroundSztafrowski, D., Suchodolski, J., Muraszko, J., Sigler, K., & Krasowska, A. (2019) · Folia Microbiologica · doi:10.1007/s12223-019-00686-3 · Cited by 12
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Self-citationBreak, T. J., Oikonomou, V., Dutzan, N., Desai, J. V., Swidergall, M., Freiwald, T., Chauss, D., Harrison, O. J., Alejo, J. C., Williams, D. W., et al. (2021) · Science · doi:10.1126/science.abi8835 · Cited by 12
“Our data point to residual type 17 cytokine activity in the mucosa of APECED patients, which may also explain the lack of mucocutaneous bacterial infections, which often occur in genetic complete IL-17RA deficiency (4).”
BackgroundDendritic cells and vaccine design for sexually-transmitted diseases
Duluc, D., Gannevat, J., Joo, H., Ni, L., Upchurch, K., Boreham, M., Carley, M., Stecher, J. A., Zurawski, G., & Oh, S. (2012) · Microbial Pathogenesis · doi:10.1016/j.micpath.2012.11.010 · Cited by 14
New Genetic Discoveries and Primary Immune Deficiencies
Hernandez-Trujillo, V. P. (2013) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-013-8380-0 · Cited by 12
“Patientswith someformsof chronicmucocutaneouscandidiasis (CMC) may have defects due to STAT 1 gain of function [58].”
BackgroundInfluentialUnmet Needs in the Treatment of Rheumatoid Arthritis
Pope, J. E., & Combe, B. G. (2013) · Open Journal of Rheumatology and Autoimmune Diseases · doi:10.4236/ojra.2013.32011 · Cited by 12
“Several different genetic disorders have been identified that result in a deficiency of IL-17RA or IL-17F or lead to autoantibody production against IL-17A and other Th17 cytokines [109-111].”
BackgroundIxekizumab for treatment of psoriasis
Dyring‐Andersen, B., Skov, L., & Zachariae, C. O. C. (2015) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2015.1023295 · Cited by 12
“Complete autosomal recessive IL-17RA deficiency, partial autosomal dominant IL-17F deficiency and mutations of adaptor protein ACT1 are genetic etiologies associated with chronic mucocutaneous candidiasis [38,39].”
BackgroundA 32-Year-Old Man With Ulcerative Mucositis, Skin Lesions, and Nail Dystrophy
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Cytokines and Cytokine Receptors
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“Дефекты генов-участников цитокинового сигнального каскада (IL17F, IL17RA, IL17RC) приводят преимущественно к развитию изолированного хронического кожно-слизистого кандидоза [33, 34].”
Comment on “Aberrant type 1 immunity drives susceptibility to mucosal fungal infections”
Puel, A., & Casanova, J. (2021) · Science · doi:10.1126/science.abi5459 · Cited by 12
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Mills, K. A. M., Aufiero, M. A., & Hohl, T. M. (2024) · Current Opinion in Microbiology · doi:10.1016/j.mib.2024.102508 · Cited by 11
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“IL-17A and IL-17F are key members of the IL-17 family and are produced predominantly by Th17 cells, although neutrophils and innate lymphoid cells can also produce these cytokines.”
BackgroundInfluentialDermatophyte Immune Memory Is Only Skin-Deep
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“Human with inborn errors of IL-17 immunity clearly impair mucocutaneous immunity to Candida albicans (Puel et al., 2011).”
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“Other disease manifestations, such as recurrent (myco-) bacterial, viral, and non-Candida fungal infections, have also been reported.”
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“Despite the lack of evidence in murine models that supports the role of IL-17F in inflammation, human genetic data from people who have autosomal dominant IL-17F mutations show that this cytokine has a hitherto underappreciated significance (Puel et al., 2011).”
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“In addition to the preceding disorders that decrease IL-17 (and selectively IL-22) production, the distinctive feature of CMC and the principal of physiologic homogeneity led to the discovery of IEI that cause impaired responses to IL-17 due to either autosomal dominant (AD) mutations in the IL-17F cytokine [54], AR m…”
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Metadata
- Authors
- Puel, A., Cypowyj, S., Bustamante, J., Wright, J. F., Liu, L., Lim, H. K., Migaud, M., Israel, L., Chrabieh, M., Audry, M., Gumbleton, M., Toulon, A., Bodemer, C., El-Baghdadi, J., Whitters, M., Paradis, T., Brooks, J., Collins, M., Wolfman, N. M., Al-Muhsen, S., Galicchio, M., Abel, L., Picard, C., & Casanova, J.-L.
- Affiliations
- Inserm (FR)
- Rockefeller University (US)
- Pfizer (United States) (US)
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, U980, and University Paris Descartes, Necker Medical School, 75015 Paris, France.
- SUNY Upstate Medical University (US)
- Hôpital Necker-Enfants Malades (FR)
- Unit of Genetics, Military Hospital of Instruction Mohamed V, Rabat 10000, Morocco.
- Prince Naif Center for Immunology Research, Department of Pediatrics, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
- Victor J. Vilela Children’s Hospital, Rosario, Santa Fe 2000, Argentina.
- Corresponding author
- Puel, Anne
- Cypowyj, Sophie
- Abel, Laurent
- Casanova, Jean-Laurent
- ORCID
- Venue
- Science
- Published
- 2011-04
- Volume
- 332
- Issue
- 6025
- Pages
- 65-68
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3070042
- OpenAlex
- W2034453891
- Cited by
- 1,056
- References
- 30
- Citations by year
- 2026: 26 · 2025: 35 · 2024: 29 · 2023: 54 · 2022: 52 · 2021: 64 · 2020: 76 · 2019: 57 · 2018: 67 · 2017: 84 · 2016: 81 · 2015: 76 · 2014: 94 · 2013: 95 · 2012: 103
- FWCI
- 49.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Research Resources (UL1RR024143)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- chronic mucocutaneous candidiasis, IL-17A, Candida albicans, primary immunodeficiency, autosomal recessive inheritance, autosomal dominant inheritance
- MeSH terms
- Candida albicans, Candidiasis, Chronic Mucocutaneous, Child, Child, Preschool, Female, Genes, Dominant, Genes, Recessive, Humans, Male, Molecular Sequence Data, Mutation, Pedigree, Signal Transduction, Interleukin-17, Receptors, Interleukin-17, Th17 Cells
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