Year: 2018
Type: article
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.
Source: Nature Communications
Authors: 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, Frank L. van de Veerdonk
Institutions: Radboud University Nijmegen, Institut Pasteur, Radboud University Medical Center, Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI), University of Minho, St. Jude Children's Research Hospital, University of Lisbon, Hospital de Santa Maria, Instituto de Medicina Molecular João Lobo Antunes, IPO Porto, Universitair Ziekenhuis Leuven, KU Leuven
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1516346500, G2440504136, G323769159, G3326568298, G3638010913, G396252163, G4316116677, G4724859719, New avenues for the development of personalized medical interventions for neurological, oncologic and surgical disorders – “PersonalizedNOS”, G5485649731, G7584003722, THE ROLE OF INFLAMMASOME ACTIVATION IN HOST IMMUNITY TO FUNGAL INFECTION - The inflammasome-microbiota interplay in antifungal immunity, G96847669
OpenAlex ID: W2809760616