Genetic deficiency of NOD2 confers resistance to invasive aspergillosis

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 Fitting, Dirk J. de Jong, João F. Lacerda, António Campos, Willem J. G. Melchers, Katrien Lagrou, Johan Maertens, Thirumala-Devi Kanneganti, Agostinho Carvalho, Oumaima Ibrahim-Granet and Frank L. Veerdonk ()
Additional contact information
Mark S. Gresnigt: Institut Pasteur
Cristina Cunha: University of Minho
Martin Jaeger: Radboud University Medical Center
Samuel M. Gonçalves: University of Minho
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
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
Johan Maertens: KU Leuven
Thirumala-Devi Kanneganti: St. Jude Children’s Research Hospital
Agostinho Carvalho: University of Minho
Oumaima Ibrahim-Granet: Institut Pasteur
Frank L. Veerdonk: Radboud University Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04912-3

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