Nature communications · 2018
Genetic deficiency of NOD2 confers resistance to invasive aspergillosis.
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Gresnigt Mark S, Cunha Cristina, Jaeger Martin, Gonçalves Samuel M, Malireddi R K Subbarao, Ammerdorffer Anne, Lubbers Rosalie, Oosting Marije, Rasid Orhan, Jouvion Grégory, Fitting Catherine, Jong Dirk J de, Lacerda João F, Campos António, Melchers Willem J G, Lagrou Katrien, Maertens Johan, Kanneganti Thirumala-Devi, Carvalho Agostinho, Ibrahim-Granet Oumaima, van de Veerdonk Frank L
Аннотация
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.