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Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity

Author

Listed:
  • Olaf Gross

    (Technische Universität München)

  • Andreas Gewies

    (Technische Universität München)

  • Katrin Finger

    (Technische Universität München)

  • Martin Schäfer

    (Technische Universität München)

  • Tim Sparwasser

    (Technische Universität München)

  • Christian Peschel

    (Technische Universität München)

  • Irmgard Förster

    (Technische Universität München
    University of Düsseldorf)

  • Jürgen Ruland

    (Technische Universität München)

Abstract

Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10–Malt1-mediated NF-κB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10–Malt1. Thus, our results define a novel innate immune pathway and indicate that evolutionarily distinct ITAM receptors in innate and adaptive immune cells use diverse adaptor proteins to engage selectively the conserved Bcl10–Malt1 module.

Suggested Citation

  • Olaf Gross & Andreas Gewies & Katrin Finger & Martin Schäfer & Tim Sparwasser & Christian Peschel & Irmgard Förster & Jürgen Ruland, 2006. "Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity," Nature, Nature, vol. 442(7103), pages 651-656, August.
    • Handle: RePEc:nat:nature:v:442:y:2006:i:7103:d:10.1038_nature04926
    DOI: 10.1038/nature04926
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    Cited by:

    1. Yao Yu & Rong-Rong Wang & Nai-Jun Miao & Jia-Jie Tang & Yun-Wei Zhang & Xiang-Ran Lu & Pei-Yi Yan & Jing Wang & Xin-Ming Jia, 2022. "PD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Alfredo Córdova-Martínez & Alberto Caballero-García & Enrique Roche & David C. Noriega, 2021. "β-Glucans Could Be Adjuvants for SARS-CoV-2 Virus Vaccines (COVID-19)," IJERPH, MDPI, vol. 18(23), pages 1-13, November.
    3. Torben Mentrup & Anna Yamina Stumpff-Niggemann & Nadja Leinung & Christine Schlosser & Katja Schubert & Rebekka Wehner & Antje Tunger & Valentin Schatz & Patrick Neubert & Ann-Christine Gradtke & Jani, 2022. "Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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