Genetic deficiency of NOD2 confers resistance to invasive aspergillosis

• Autor(a) principal: Gresnigt, Mark S.
• Data de Publicação: 2018
• Outros Autores: Cunha, Cristina, Jaeger, Martin, Gonçalves, Samuel Martins, 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, Veerdonk, Frank L. van de
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/58098
• topic: Animals; Aspergillosis; Aspergillus; Cytokines; Female; Hematopoietic Stem Cell Transplantation; Humans; Lectins, C-Type; Lung; Male; Mice, Inbred C57BL; Microbial Viability; Nod2 Signaling Adaptor Protein; Paranasal Sinuses; Phagocytosis; Polymorphism, Single Nucleotide; Risk Factors; Disease Resistance; Science & Technology

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.