A nod to the bond between NOD2 and mycobacteria

• Published in: PLoS pathogens 2023-06, Vol.19 (6), p.e1011389
• Main Authors: Dubé, Jean-Yves, Behr, Marcel A
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Animal diseases; Animal health; Animals; Bacteria; Bacterial infections; Biology and Life Sciences; Cell walls; Control; Crohn's disease; Crohns disease; Cytokines - metabolism; Enzymes; Epidemiology; Humans; Identification and classification; Immune response; Immune system; Immunization; Immunotherapy; Infection; Infections; Kinases; Leprosy; Ligands; MAP kinase; Medicine and Health Sciences; Mice; Mutation; Mycobacteria; Mycobacterium; Mycobacterium - metabolism; Mycobacterium Infections; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; NOD2 protein; Nod2 Signaling Adaptor Protein - genetics; Pattern recognition; Pattern recognition receptors; Peptides; Prevention; Research and Analysis Methods; Review; Risk factors; Signal Transduction - physiology; Tuberculosis
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1011389

Mycobacteria are responsible for several human and animal diseases. NOD2 is a pattern recognition receptor that has an important role in mycobacterial recognition. However, the mechanisms by which mutations in NOD2 alter the course of mycobacterial infection remain unclear. Herein, we aimed to review the totality of studies directly addressing the relationship between NOD2 and mycobacteria as a foundation for moving the field forward. NOD2 was linked to mycobacterial infection at 3 levels: (1) genetic, through association with mycobacterial diseases of humans; (2) chemical, through the distinct NOD2 ligand in the mycobacterial cell wall; and (3) immunologic, through heightened NOD2 signaling caused by the unique modification of the NOD2 ligand. The immune response to mycobacteria is shaped by NOD2 signaling, responsible for NF-κB and MAPK activation, and the production of various immune effectors like cytokines and nitric oxide, with some evidence linking this to bacteriologic control. Absence of NOD2 during mycobacterial infection of mice can be detrimental, but the mechanism remains unknown. Conversely, the success of immunization with mycobacteria has been linked to NOD2 signaling and NOD2 has been targeted as an avenue of immunotherapy for diseases even beyond mycobacteria. The mycobacteria-NOD2 interaction remains an important area of study, which may shed light on immune mechanisms in disease.