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Genetic deficiency of NOD2 confers resistance to invasive aspergillosis

Author

Listed:
  • Mark S. Gresnigt

    (Institut Pasteur
    Radboud University Medical Center
    Hans Knöll Institute)

  • Cristina Cunha

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães)

  • Martin Jaeger

    (Radboud University Medical Center)

  • Samuel M. Gonçalves

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães)

  • R. K. Subbarao Malireddi

    (St. Jude Children’s Research Hospital)

  • Anne Ammerdorffer

    (Radboud University Medical Center)

  • Rosalie Lubbers

    (Radboud University Medical Center)

  • Marije Oosting

    (Radboud University Medical Center)

  • Orhan Rasid

    (Institut Pasteur)

  • Grégory Jouvion

    (Unité Histopathologie Humaine et Modèles Animaux, Institut Pasteur)

  • Catherine Fitting

    (Institut Pasteur)

  • Dirk J. de Jong

    (Radboud University Medical Center)

  • João F. Lacerda

    (Faculdade de Medicina de Lisboa, Universidade de Lisboa
    Serviço de Hematologia e Transplantação de Medula, Hospital de Santa Maria)

  • António Campos

    (Serviço de Transplantação de Medula Óssea (STMO), Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino de Almeida)

  • Willem J. G. Melchers

    (Nijmegen, the Netherlands)

  • Katrien Lagrou

    (KU Leuven
    University Hospitals Leuven)

  • Johan Maertens

    (KU Leuven
    University Hospitals Leuven)

  • Thirumala-Devi Kanneganti

    (St. Jude Children’s Research Hospital)

  • Agostinho Carvalho

    (University of Minho
    ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães)

  • Oumaima Ibrahim-Granet

    (Institut Pasteur)

  • Frank L. Veerdonk

    (Radboud University Medical Center)

Abstract

Invasive aspergillosis (IA) is a severe infection that can occur in severely immunocompromised patients. Efficient immune recognition of Aspergillus is crucial to protect against infection, and previous studies suggested a role for NOD2 in this process. However, thorough investigation of the impact of NOD2 on susceptibility to aspergillosis is lacking. Common genetic variations in NOD2 has been associated with Crohn’s disease and here we investigated the influence of these genetic variations on the anti-Aspergillus host response. A NOD2 polymorphism reduced the risk of IA after hematopoietic stem-cell transplantation. Mechanistically, absence of NOD2 in monocytes and macrophages increases phagocytosis leading to enhanced fungal killing, conversely, NOD2 activation reduces the antifungal potential of these cells. Crucially, Nod2 deficiency results in resistance to Aspergillus infection in an in vivo model of pulmonary aspergillosis. Collectively, our data demonstrate that genetic deficiency of NOD2 plays a protective role during Aspergillus infection.

Suggested Citation

  • Mark S. Gresnigt & Cristina Cunha & Martin Jaeger & Samuel M. Gonçalves & R. K. Subbarao Malireddi & Anne Ammerdorffer & Rosalie Lubbers & Marije Oosting & Orhan Rasid & Grégory Jouvion & Catherine Fi, 2018. "Genetic deficiency of NOD2 confers resistance to invasive aspergillosis," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04912-3
    DOI: 10.1038/s41467-018-04912-3
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