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Nucleotide-Binding Oligomerization Domain 2 Contributes to Limiting Growth of Mycobacterium abscessus in the Lung of Mice by Regulating Cytokines and Nitric Oxide Production

Title
Nucleotide-Binding Oligomerization Domain 2 Contributes to Limiting Growth of Mycobacterium abscessus in the Lung of Mice by Regulating Cytokines and Nitric Oxide Production
Authors
Lee, Jun-YoungLee, Moo-SeungKim, Dong JaeYang, Soo-JinLee, Sang-JinNoh, Eui-JeongShin, Sung JaePark, Jong-Hwan
DGIST Authors
Kim, Dong Jae
Issue Date
2017-11
Citation
Frontiers in Immunology, 8
Type
Article
Article Type
Article
Keywords
TUMOR-NECROSIS-FACTORHOST-DEFENSETUBERCULOSIS INFECTIONBACTERIAL-INFECTIONMURAMYL DIPEPTIDEHUMAN MACROPHAGESGAMMA-INTERFERONIMMUNE-RESPONSENOD2INNATE
ISSN
1664-3224
Abstract
Mycobacterium abscessus is a prominent cause of pulmonary infection in immunosuppressed patients and those with cystic fibrosis. Nucleotide-binding oligomerization domain (NOD) 2 is a cytosolic receptor which senses a bacterial peptidoglycan component, muramyl dipeptide (MDP). Although nucleotide-binding oligomerization domain 2 (NOD2) contributes to protect host against various microbial infections, it is still unclear whether NOD2 is essential to regulate host immune responses against M. abscessus infection. In this study, we sought to clarify the role of NOD2 and the underlying mechanism in host defense against M. abscessus infection. Mice were infected intranasally with M. abscessus and sacrificed at indicated time points. Bacterial survival, cytokines production, and pathology in the lungs were determined. Bone marrow-derived macrophages were used to clarify cellular mechanism of NOD2-mediated immune response. Bacterial clearance was impaired, and pathology was more severe in the lungs of NOD2-deficient mice compared with the wild-type mice. In macrophages, NOD2-mediated activation of p38 and JNK were required for production of proinflammatory cytokines and nitric oxide (NO) and expression of iNOS in response to M. abscessus. NO was critical for limiting intracellular growth of the pathogen. Intranasal administration of MDP reduced in vivo bacterial replication and thus improved lung pathology in M. abscessus-infected mice. This study offers important new insights into the potential roles of the NOD2 in initiating and potentiating innate immune response against M. abscessus pulmonary infection. © 2017 Lee, Lee, Kim, Yang, Lee, Noh, Shin and Park.
URI
http://hdl.handle.net/20.500.11750/4842
DOI
10.3389/fimmu.2017.01477
Publisher
Frontiers Media S.A.
Related Researcher
Files:
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Collection:
Laboratory Animal Resource Center1. Journal Articles


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