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https://hdl.handle.net/1822/58098
Título: | Genetic deficiency of NOD2 confers resistance to invasive aspergillosis |
Autor(es): | Gresnigt, Mark S. 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 |
Palavras-chave: | 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 |
Data: | 2018 |
Editora: | Nature Publishing Group |
Revista: | Nature Communications |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/58098 |
DOI: | 10.1038/s41467-018-04912-3 |
ISSN: | 2041-1723 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Genetic deficiency of NOD2 confers resistance to invasive aspergillosis.pdf | 3,37 MB | Adobe PDF | Ver/Abrir |