Marcel A Behr1, Maziar Divangahi2. 1. Department of Medicine, McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada; McGill International TB Centre, Montreal H3G 1A4, Canada. Electronic address: marcel.behr@mcgill.ca. 2. Department of Medicine, McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada; McGill International TB Centre, Montreal H3G 1A4, Canada; Meakins-Christie Laboratories, 3626 St. Urbain Street, Montreal H2X 2P2, Canada.
Abstract
PURPOSE: Mycobacterium tuberculosis contributed to the discovery of delayed-type hypersensitivity and cell-mediated immunity. However, the biochemical basis for the immunogenicity of the mycobacterial cell wall has until recently remained unknown. RECENT FINDINGS: Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) responds to bacterial peptidolycan-derived muramyl dipeptide (MDP). Whereas most bacteria produce N-acetyl MDP, mycobacteria produce an unusual modified form of MDP, called N-glycolyl MDP. Disruption of N-glycolyl MDP synthesis in mycobacteria greatly diminishes the contribution of NOD2 to mycobacterial sensing. Additionally, N-glycolyl MDP is more potent and efficacious than N-acetyl MDP at inducing innate responses and T cell-mediated immunity. SUMMARY: The sensitivity of NOD2 to the mycobacterial peptidoglycan may link the natural history of both innate and adaptive immunity to mycobacterial infection.
PURPOSE:Mycobacterium tuberculosis contributed to the discovery of delayed-type hypersensitivity and cell-mediated immunity. However, the biochemical basis for the immunogenicity of the mycobacterial cell wall has until recently remained unknown. RECENT FINDINGS: Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) responds to bacterial peptidolycan-derived muramyl dipeptide (MDP). Whereas most bacteria produce N-acetyl MDP, mycobacteria produce an unusual modified form of MDP, called N-glycolyl MDP. Disruption of N-glycolyl MDP synthesis in mycobacteria greatly diminishes the contribution of NOD2 to mycobacterial sensing. Additionally, N-glycolyl MDP is more potent and efficacious than N-acetyl MDP at inducing innate responses and T cell-mediated immunity. SUMMARY: The sensitivity of NOD2 to the mycobacterial peptidoglycan may link the natural history of both innate and adaptive immunity to mycobacterial infection.
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