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Title: Nod2 is required for the early innate immune clearance of Acinetobacter baumannii from the lungs
Authors: Kale S.D. 
Dikshit N. 
Kumar P. 
Balamuralidhar V. 
Khameneh H.J.
Bin Abdul Malik N. 
Koh T.H. 
Tan G.G.Y.
Tan T.T. 
Mortellaro A.
Sukumaran B. 
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Kale S.D., Dikshit N., Kumar P., Balamuralidhar V., Khameneh H.J., Bin Abdul Malik N., Koh T.H., Tan G.G.Y., Tan T.T., Mortellaro A., Sukumaran B. (2017). Nod2 is required for the early innate immune clearance of Acinetobacter baumannii from the lungs. Scientific Reports 7 (1) : 17429. ScholarBank@NUS Repository.
Abstract: Acinetobacter baumannii (A. baumannii) is a significant cause of severe nosocomial pneumonia in immunocompromised individuals world-wide. With limited treatment options available, a better understanding of host immnity to A. baumannii infection is critical to devise alternative control strategies. Our previous study has identified that intracellular Nod1/Nod2 signaling pathway is required for the immune control of A. baumannii in airway epithelial cells in vitro. In the current study, using Nod2-/- mice and an in vivo sublethal model of pulmonary infection, we show that Nod2 contributes to the early lung defense against A. baumannii infection through reactive oxygen species (ROS)/reactive nitrogen species (RNS) production as Nod2-/- mice showed significantly reduced production of ROS/RNS in the lungs following A. baumannii infection. Consistent with the higher bacterial load, A. baumannii-induced neutrophil recruitment, cytokine/chemokine response and lung pathology was also exacerbated in Nod2-/- mice at early time points post-infection. Finally, we show that administration of Nod2 ligand muramyl dipeptide (MDP) prior to infection protected the wild- type mice from A. baumannii pulmonary challenge. Collectively, Nod2 is an important player in the early lung immunity against A. baumannii and modulating Nod2 pathway could be considered as a viable therapeutic strategy to control A. baumannii pulmonary infection. © 2017 The Author(s).
Source Title: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-017-17653-y
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