Nod2 is required for the early innate immune clearance of Acinetobacter baumannii from the lungs

被引：22

作者：

Kale, Sandeep D. ^{[1
]}

Dikshit, Neha ^{[1
]}

Kumar, Pankaj ^{[1
]}

Balamuralidhar, Vanniarajan ^{[1
]}

Khameneh, Hanif Javanmard ^{[2
]}

Malik, Najib Bin Abdul ^{[1
]}

Koh, Tse Hsien ^{[3
]}

Tan, Gladys Gek Yen ^{[4
]}

Thuan Tong Tan ^{[5
]}

Mortellaro, Alessandra ^{[2
]}

Sukumaran, Bindu ^{[1
]}

机构：

[1] Duke NUS Med Sch, Program Emerging Infect Dis, Singapore 169857, Singapore

[2] ASTAR, Singapore Immunol Network SIgN, Singapore 138648, Singapore

[3] Singapore Gen Hosp, Div Pathol, Dept Microbiol, Singapore, Singapore

[4] DSO Natl Labs, Singapore, Singapore

[5] Singapore Gen Hosp, Dept Infect Dis, Singapore, Singapore

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

INFECTION; MICE; MURABUTIDE; CONTRIBUTES; NEUTROPHILS; RESISTANCE; DIPEPTIDE; DEFENSE; CD14;

D O I：

10.1038/s41598-017-17653-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9