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

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.