Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/58098

TitleGenetic deficiency of NOD2 confers resistance to invasive aspergillosis
Author(s)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
KeywordsAnimals
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
Issue date2018
PublisherNature Publishing Group
JournalNature Communications
Abstract(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.
TypeArticle
URIhttp://hdl.handle.net/1822/58098
DOI10.1038/s41467-018-04912-3
ISSN2041-1723
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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