BACKGROUND: Nucleotide-binding oligomerizing domain-1 (NOD1) is a cytoplasmic 
receptor involved in recognizing bacterial peptidoglycan fragments that localize 
to the cytosol. NOD1 activation triggers inflammation, antimicrobial mechanisms 
and autophagy in both epithelial cells and murine macrophages. NOD1 mediates 
intracellular pathogen clearance in the lungs of mice; however, little is known 
about NOD1's role in human alveolar macrophages (AMs) or its involvement in 
Mycobacterium tuberculosis (Mtb) infection.
METHODS: AMs, monocytes (MNs), and monocyte-derived macrophages (MDMs) from 
healthy subjects were assayed for NOD1 expression. Cells were stimulated with 
the NOD1 ligand Tri-DAP and cytokine production and autophagy were assessed. 
Cells were infected with Mtb and treated with Tri-DAP post-infection. CFUs 
counting determined growth control, and autophagy protein recruitment to 
pathogen localization sites was analyzed by immunoelectron microscopy.
RESULTS: NOD1 was expressed in AMs, MDMs and to a lesser extent MNs. Tri-DAP 
stimulation induced NOD1 up-regulation and a significant production of IL1β, 
IL6, IL8, and TNFα in AMs and MDMs; however, the level of NOD1-dependent 
response in MNs was limited. Autophagy activity determined by expression of 
proteins Atg9, LC3, IRGM and p62 degradation was induced in a NOD1-dependent 
manner in AMs and MDMs but not in MNs. Infected AMs could be activated by 
stimulation with Tri-DAP to control the intracellular growth of Mtb. In 
addition, recruitment of NOD1 and the autophagy proteins IRGM and LC3 to the Mtb 
localization site was observed in infected AMs after treatment with Tri-DAP.
CONCLUSIONS: NOD1 is involved in AM and MDM innate responses, which include 
proinflammatory cytokines and autophagy, with potential implications in the 
killing of Mtb in humans.