Genetic deficiency of NOD2 confers resistance to invasive aspergillosis.
Genetic deficiency of NOD2 confers resistance to invasive aspergillosis.
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NOD2的遗传缺陷赋予对侵袭性曲霉病的抗性。
DOI：
10.1038/s41467-018-04912-3
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发表时间：
2018-07-06
影响因子：
16.6
通讯作者：
van de Veerdonk FL
中科院分区：
文献类型：
--
作者：
Gresnigt MS;Cunha C;Jaeger M;Gonçalves SM;Malireddi RKS;Ammerdorffer A;Lubbers R;Oosting M;Rasid O;Jouvion G;Fitting C;Jong DJ;Lacerda JF;Campos A Jr;Melchers WJG;Lagrou K;Maertens J;Kanneganti TD;Carvalho A;Ibrahim-Granet O;van de Veerdonk FL
侵袭性曲霉病（IA）是一种严重的感染，可发生在严重免疫功能低下的患者。有效的免疫识别曲霉对预防感染至关重要，先前的研究表明NOD2在这一过程中起作用。然而，NOD2对曲霉病易感性的影响尚缺乏深入的研究。NOD2的常见遗传变异与克罗恩病有关，在这里，我们研究了这些遗传变异对抗曲霉宿主反应的影响。NOD2多态性降低了造血干细胞移植后IA的风险。从机制上讲，单核细胞和巨噬细胞中NOD2的缺失增加了吞噬作用，从而增强了真菌的杀伤作用，相反，NOD2的激活降低了这些细胞的抗真菌潜能。关键是，在肺曲霉病的体内模型中，Nod2缺乏导致对曲霉感染的抵抗。总的来说，我们的数据表明NOD2的遗传缺陷在曲霉感染期间起保护作用。NOD2已被证明对曲霉感染的免疫识别至关重要。本文作者表明，由于单核细胞和巨噬细胞抗真菌活性增强，与克罗恩病相关的常见NOD2遗传变异与疾病风险降低相关。
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. NOD2 has been shown to be crucial for immune recognition of Aspergillus infection. Here the authors show that a common NOD2 genetic variant associated with Crohn’s disease is associated with reduced risk of disease due to enhanced antifungal activates of monocytes and macrophages.
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影响因子：
4.4
作者：
Gresnigt, Mark S.;Becker, Katharina L.;van de Veerdonk, Frank L.
通讯作者：
van de Veerdonk, Frank L.
影响因子：
4.8
作者：
Girardin, SE;Travassos, LH;Mengin-Lecreulx, D
通讯作者：
Mengin-Lecreulx, D
DOI：
10.1111/j.1749-6632.2012.06759.x
发表时间：
2012-01-01
期刊：
ADVANCES AGAINST ASPERGILLOSIS II
影响因子：
--
作者：
Gresnigt, Mark S.;Netea, Mihai G.;van de Veerdonk, Frank L.
通讯作者：
van de Veerdonk, Frank L.
影响因子：
6.4
作者：
Austin, Celest M.;Ma, Xin;Graviss, Edward A.
通讯作者：
Graviss, Edward A.
影响因子：
4.4
作者：
Dubourdeau, Marc;Athman, Rafika;Ibrahim-Granet, Oumaima
通讯作者：
Ibrahim-Granet, Oumaima