Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
Open accessAbstract
The C-type lectin dectin-1 binds to yeast and signals through the kinase Syk and the adaptor CARD9 to induce production of interleukin 10 (IL-10) and IL-2 in dendritic cells (DCs). However, whether this pathway promotes full DC activation remains unclear. Here we show that dectin-1-Syk-CARD9 signaling induced DC maturation and the secretion of proinflammatory cytokines, including IL-6, tumor necrosis factor and IL-23, but little IL-12. Dectin-1-activated DCs 'instructed' the differentiation of CD4+ IL-17-producing effector T cells (T(H)-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of T(H)-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent T(H)-17 responses to the organism. Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of T(H)-17 responses to some pathogens.
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The C-type lectin receptor adaptor molecule Card9 promotes IL-17+ T cell responses to some fungal pathogens but not to C. auris.
“The C-type lectin receptor adaptor molecule Card9 was found to promote IL-17+ T cell responses to some fungal pathogens but not to C. auris,6,34”
From Skin-resident T cells play an important role in controlling skin colonization of Candidozyma (Candida) auris (2026) · cites this paper as [34]
Cites
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992 · see citing works
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145 · see citing works
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605 · see citing works
Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.002 · Cited by 1,422 · see citing works
Requirement of Interleukin‐17A for Systemic Anti– <i>Candida albicans</i> Host Defense in Mice
Huang, W., Na, L., Fidel, P. L., & Schwarzenberger, P. (2004) · The Journal of Infectious Diseases · doi:10.1086/422329 · Cited by 859 · see citing works
T Cell Vaccination in Mice with Invasive Pulmonary Aspergillosis
Cenci, E., Mencacci, A., Bacci, A., Bistoni, F., Kurup, V. P., & Romani, L. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.1.381 · Cited by 223 · see citing works
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Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873 · see citing works
Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A., & Sallusto, F. (2007) · Nature Immunology · doi:10.1038/ni1496 · Cited by 1,857 · see citing works
Romani, L. (2011) · Nature Reviews Immunology · doi:10.1038/nri2939 · Cited by 1,793 · see citing works
Plasticity of CD4+ T Cell Lineage Differentiation
Zhou, L., Chong, M. M. W., & Littman, D. R. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.001 · Cited by 1,551 · see citing works
The SYK tyrosine kinase: A crucial player in diverse biological functions
Mócsai, A., Ruland, J., & Tybulewicz, V. L. J. (2010) · Nature Reviews Immunology · doi:10.1038/nri2765 · Cited by 1,368 · see citing works
Self-citationFunctional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289 · see citing works
Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis
Iliev, I. D., Funari, V. A., Taylor, K. D., Nguyen, Q., Reyes, C. N., Strom, S. P., Brown, J., Becker, C. A., Fleshner, P. R., Dubinsky, M., et al. (2012) · Science · doi:10.1126/science.1221789 · Cited by 1,073 · see citing works
Self-citationConti, H. R., Shen, F., Nayyar, N., Stocum, E., Sun, J. N., Lindemann, M. J., Ho, A. W., Hai, J. H., Yu, J. J., Jung, J. W., et al. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081463 · Cited by 1,024 · see citing works
Ishigame, H., Kakuta, S., Nagai, T., Kadoki, M., Nambu, A., Komiyama, Y., Fujikado, N., Tanahashi, Y., Akitsu, A., Kotaki, H., et al. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.009 · Cited by 1,004 · see citing works
An integrated model of the recognition of Candida albicans by the innate immune system
Netea, M. G., Brown, G. D., Kullberg, B. J., & Gow, N. A. R. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1815 · Cited by 946 · see citing works
Self-citationVolpe, E., Servant, N., Zollinger, R., Bogiatzi, S. I., Hupé, P., Barillot, E., & Soumelis, V. (2008) · Nature Immunology · doi:10.1038/ni.1613 · Cited by 938 · see citing works
Martin, B., Hirota, K., Cua, D. J., Stockinger, B., & Veldhoen, M. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.020 · Cited by 822 · see citing works
A Homozygous <i>CARD9</i> Mutation in a Family with Susceptibility to Fungal Infections
Glocker, E.-O., Hennigs, A., Nabavi, M., Schäffer, A. A., Woellner, C., Salzer, U., Pfeifer, D., Veelken, H., Warnatz, K., Tahami, F., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810719 · Cited by 800 · see citing works
Self-citationIdentification of a dendritic cell receptor that couples sensing of necrosis to immunity
Sancho, D., Joffre, O. P., Keller, A. M., Rogers, N. C., Martínez, D., Hernanz-Falcón, P., Rosewell, I., & Sousa, C. R. E. (2009) · Nature · doi:10.1038/nature07750 · Cited by 750 · see citing works
Self-citationHuman dectin-1 deficiency and mucocutaneous fungal infections
Ferwerda, B., Ferwerda, G., Plantinga, T. S., Willment, J. A., van Spriel, A. B., Venselaar, H., Elbers, C. C., Johnson, M. D., Cambi, A., Huysamen, C., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0901053 · Cited by 752 · see citing works
Self-citationDeficiency of Th17 cells in hyper IgE syndrome due to mutations in <i>STAT3</i>
Ma, C. S., Chew, G. Y. J., Simpson, N., Priyadarshi, A., Wong, M., Grimbacher, B., Fulcher, D. A., Tangye, S. G., & Cook, M. C. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080218 · Cited by 652 · see citing works
C-type lectin receptors orchestrate antifungal immunity
Hardison, S. E., & Brown, G. D. (2012) · Nature Immunology · doi:10.1038/ni.2369 · Cited by 460 · see citing works
Self-citationInnate immune recognition of infected apoptotic cells directs TH17 cell differentiation
Torchinsky, M. B., Garaude, J., Martin, A. P., & Blander, J. M. (2009) · Nature · doi:10.1038/nature07781 · Cited by 364 · see citing works
Th17 cells in immunity to Candida albicans
Hernández-Santos, N., & Gaffen, S. L. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.04.008 · Cited by 361 · see citing works
Hu, X., Chakravarty, S. D., & Ivashkiv, L. B. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00707.x · Cited by 303 · see citing works
Sparber, F., De Gregorio, C., Steckholzer, S., Ferreira, F. M., Dolowschiak, T., Ruchti, F., Kirchner, F. R., Mertens, S., Prinz, I., Joller, N., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.02.002 · Cited by 255 · see citing works
Self-citationPlantinga, T. S., van der Velden, W. J. F. M., Ferwerda, B., van Spriel, A. B., Adema, G., Feuth, T., Donnelly, J. P., Brown, G. D., Kullberg, B., Blijlevens, N. M. A., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/604714 · Cited by 247 · see citing works
Self-citationMartínez-López, M., Iborra, S., Conde-Garrosa, R., Mastrangelo, A., Danne, C., Mann, E. R., Reid, D. M., Gaboriau-Routhiau, V., Chaparro, M., Lorenzo, M. P., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.020 · Cited by 228 · see citing works
Self-citationThe role of Syk/CARD9 coupled C-type lectins in antifungal immunity
Drummond, R. A., Saijo, S., Iwakura, Y., & Brown, G. D. (2011) · European Journal of Immunology · doi:10.1002/eji.201041252 · Cited by 221 · see citing works
Self-citationKagami, S., Rizzo, H. L., Kurtz, S. E., Miller, L. S., & Blauvelt, A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001153 · Cited by 216 · see citing works
IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells
Bär, E., Whitney, P. G., Moor, K., Reis e Sousa, C., & LeibundGut-Landmann, S. (2014) · Immunity · doi:10.1016/j.immuni.2013.12.002 · Cited by 197 · see citing works
Syk-coupled C-type lectins in immunity
Kerrigan, A. M., & Brown, G. D. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.01.002 · Cited by 170 · see citing works
Self-citationHost–microbe interactions: innate pattern recognition of fungal pathogens
van de Veerdonk, F. L., Kullberg, B. J., van der Meer, J. W., Gow, N. A., & Netea, M. G. (2008) · Current Opinion in Microbiology · doi:10.1016/j.mib.2008.06.002 · Cited by 169 · see citing works
Lionakis, M. S., Iliev, I. D., & Hohl, T. M. (2017) · JCI Insight · doi:10.1172/jci.insight.93156 · Cited by 153 · see citing works
Huang, X., Hurabielle, C., Drummond, R. A., Bouladoux, N., Desai, J. V., Sim, C. K., Belkaid, Y., Lionakis, M. S., & Segre, J. A. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2020.12.002 · Cited by 144 · see citing works
Fei, M., Bhatia, S., Oriss, T. B., Yarlagadda, M., Khare, A., Akira, S., Saijo, S., Iwakura, Y., Fallert Junecko, B. A., Reinhart, T. A., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015476108 · Cited by 127 · see citing works
Bi, L., Gojestani, S., Wu, W., Hsu, Y.-M. S., Zhu, J., Ariizumi, K., & Lin, X. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.131300 · Cited by 126 · see citing works
Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion
Pradhan, A., Avelar, G. M., Bain, J. M., Childers, D., Pelletier, C., Larcombe, D. E., Shekhova, E., Netea, M. G., Brown, G. D., Erwig, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13298-9 · Cited by 119 · see citing works
Self-citationOral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis
Aggor, F. E. Y., Break, T. J., Trevejo-Nuñez, G., Whibley, N., Coleman, B. M., Bailey, R. D., Kaplan, D. H., Naglik, J. R., Shan, W., Shetty, A. C., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.aba0570 · Cited by 119 · see citing works
Kunzmann, L. K., Schoknecht, T., Poch, T., Henze, L., Stein, S., Kriz, M., Grewe, I., Preti, M., Hartl, J., Pannicke, N., et al. (2020) · Hepatology · doi:10.1002/hep.31140 · Cited by 93 · see citing works
The role of the cell wall in fungal pathogenesis
Arana, D. M., Prieto, D., Román, E., Nombela, C., Alonso‐Monge, R., & Pla, J. (2009) · Microbial Biotechnology · doi:10.1111/j.1751-7915.2008.00070.x · Cited by 92 · see citing works
Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells
Kumaresan, P. R., da Silva, T. A., & Kontoyiannis, D. P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01939 · Cited by 85 · see citing works
Grimm, M. J., Vethanayagam, R. R., Almyroudis, N. G., Dennis, C. G., Khan, A. N. H., D’Auria, A. C., Singel, K. L., Davidson, B. A., Knight, P. R., Blackwell, T. S., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202800 · Cited by 81 · see citing works
van den Berg, L. M., Zijlstra-Willems, E. M., Richters, C. D., Ulrich, M. M. W., & Geijtenbeek, T. B. H. (2014) · Cellular Immunology · doi:10.1016/j.cellimm.2014.03.007 · Cited by 65 · see citing works
Galectin-3 Modulates Th17 Responses by Regulating Dendritic Cell Cytokines
Fermin Lee, A., Chen, H.-Y., Wan, L., Wu, S.-Y., Yu, J.-S., Huang, A. C., Miaw, S.-C., Hsu, D. K., Wu-Hsieh, B. A., & Liu, F.-T. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.06.017 · Cited by 63 · see citing works
C-type lectin receptor-mediated immune recognition and response of the microbiota in the gut
Li, T.-H., Liu, L., Hou, Y.-Y., Shen, S.-N., & Wang, T.-T. (2019) · Gastroenterology Report · doi:10.1093/gastro/goz028 · Cited by 58 · see citing works
van de Veerdonk, F. L., Kullberg, B. J., Verschueren, I. C., Hendriks, T., van der Meer, J. W. M., Joosten, L. A. B., & Netea, M. G. (2010) · Shock · doi:10.1097/shk.0b013e3181d67041 · Cited by 49 · see citing works
Immune responses to airborne fungi and non-invasive airway diseases
Vacher, G., Niculita-Hirzel, H., & Roger, T. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-014-0471-3 · Cited by 33 · see citing works
The skin mycobiome and intermicrobial interactions in the cutaneous niche
Tuor, M., & LeibundGut-Landmann, S. (2023) · Current Opinion in Microbiology · doi:10.1016/j.mib.2023.102381 · Cited by 30 · see citing works
Self-citationFirinu, D., Massidda, O., Lorrai, M. M., Serusi, L., Peralta, M., Barca, M. P., Serra, P., & Manconi, P. E. (2011) · Clinical and Developmental Immunology · doi:10.1155/2011/283239 · Cited by 23 · see citing works
Zhao, W., Wang, X., Zhao, C., & Yan, Z. (2021) · Microbial Pathogenesis · doi:10.1016/j.micpath.2021.104988 · Cited by 9 · 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
Xie, J., Yan, L., Kadosh, D., & Xiong, N. (2026) · iScience · doi:10.1016/j.isci.2026.115862 · Cited by 1 · see citing works
- Authors
- LeibundGut-Landmann, S., Groß, O., Robinson, M. J., Osorio, F., Slack, E. C., Tsoni, S. V., Schweighoffer, E., Tybulewicz, V., Brown, G. D., Ruland, J., & Reis e Sousa, C.
- Affiliations
- TUM Klinikum (DE)
- Cancer Research UK (GB)
- University of Cape Town (ZA)
- National Institute for Medical Research (GB)
- Venue
- Nature Immunology
- Published
- 2007-04-22
- Volume
- 8
- Issue
- 6
- Pages
- 630-638
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1964465182
- Cited by
- 1,191
- References
- 6
- Citations by year
- 2026: 34 · 2025: 34 · 2024: 33 · 2023: 31 · 2022: 35 · 2021: 33 · 2020: 51 · 2019: 43 · 2018: 47 · 2017: 53 · 2016: 53 · 2015: 62 · 2014: 70 · 2013: 69 · 2012: 94
- FWCI
- 43.28
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Wellcome Trust (086558)
- Cancer Research UK
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (106884)
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- Dectin-1, Syk, CARD9, Th17 cells, dendritic cell maturation, innate immunity, Candida albicans, IL-23, IL-17, Th1 cells, adjuvants, C-type lectin receptor signaling
- MeSH terms
- Syk Kinase, Dectin-1, Adjuvants, Immunologic, Animals, Antibody Formation, Candida albicans, Cell Differentiation, Cells, Cultured, Dendritic Cells, T-Lymphocytes, Helper-Inducer, Immunity, Innate, Membrane Proteins, Nerve Tissue Proteins, Protein-Tyrosine Kinases, Signal Transduction, Mice, Knockout, Interleukin-17, Lectins, C-Type, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, CARD Signaling Adaptor Proteins
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