Nucleotide-oligomerizing domain-1 (NOD1) receptor activation induces pro-inflammatory responses and autophagy in human alveolar macrophages

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 media...

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Bibliographic Details
Published in:	BMC pulmonary medicine Vol. 14; no. 1; p. 152
Main Authors:	Juárez, Esmeralda, Carranza, Claudia, Hernández-Sánchez, Fernando, Loyola, Elva, Escobedo, Dante, León-Contreras, Juan Carlos, Hernández-Pando, Rogelio, Torres, Martha, Sada, Eduardo
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 25-09-2014 BioMed Central
Subjects:	Analysis Antimicrobial agents Autophagy Autophagy - drug effects Cells, Cultured Chemokines Colony Count, Microbial Cytokines Cytokines - metabolism Diaminopimelic Acid - analogs & derivatives Diaminopimelic Acid - pharmacology Gene expression GTP-Binding Proteins - metabolism Humans Immunity, Innate Kinases Ligands Macrophages Macrophages, Alveolar - drug effects Macrophages, Alveolar - metabolism Macrophages, Alveolar - microbiology Microtubule-Associated Proteins - metabolism Molecular biology Monocytes - drug effects Monocytes - metabolism Monocytes - microbiology Mortality Mycobacterium tuberculosis Mycobacterium tuberculosis - growth & development Nod1 Signaling Adaptor Protein - metabolism Oligopeptides - pharmacology Physiological aspects Proteins Pulmonology Streptococcus infections Studies Tuberculosis Tuberculosis, Pulmonary - metabolism Up-Regulation - drug effects
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Summary:	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. 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2466 1471-2466
DOI:	10.1186/1471-2466-14-152