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MAP - NOD2 study

 
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Reef08



Joined: 28 Jan 2008
Posts: 14

PostPosted: Fri Jul 10, 2009 3:21 am    Post subject: MAP - NOD2 study Reply with quote

http://www.eurekalert.org/pub_releases/2009-07/muhc-tae070909.php

Quote:
When the NOD2 gene functions normally, it codes for a receptor that will recognize invading bacteria and then trigger the immune response. This study demonstrates that the NOD2 receptor preferentially recognizes a peptide called N-glycolyl-MDP, which is only found in a specific family of bacteria called mycobacteria. When mycobacteria invade the human body, they cause an immediate and very strong immune response via the NOD2 receptor.



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david.crichton



Joined: 02 May 2008
Posts: 83

PostPosted: Fri Jul 10, 2009 4:36 pm    Post subject: haha Reply with quote

Haha, you beat me to it!

This strongly points to MAP not being a "secondary invader".

Here is a copy of PubMed abstract:

The Journal of Experimental Medicine 2009 Jul 6. [Epub ahead of print]

Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide.

Coulombe F, Divangahi M, Veyrier F, de Léséleuc L, Gleason JL, Yang Y, Kelliher MA, Pandey AK, Sassetti CM, Reed MB, Behr MA.

Department of Medicine, McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada.

   Peptidoglycan-derived muramyl dipeptide (MDP) activates innate immunity via the host sensor NOD2. Although MDP is N-acetylated in most bacteria, mycobacteria and related Actinomycetes convert their MDP to an N-glycolylated form through the action of N-acetyl muramic acid hydroxylase (NamH). We used a combination of bacterial genetics and synthetic chemistry to investigate whether N-glycolylation of MDP alters NOD2-mediated immunity. Upon infecting macrophages with 12 bacteria, tumor necrosis factor (TNF) alpha secretion was NOD2 dependent only with mycobacteria and other Actinomycetes (Nocardia and Rhodococcus). Disruption of namH in Mycobacterium smegmatis obrogated NOD2-mediated TNF secretion, which could be restored upon gene complementation. In mouse macrophages, N-glycolyl MDP was more potent than N-acetyl MDP at activating RIP2, nuclear factor kappaB, c-Jun N-terminal kinase, and proinflammatory cytokine secretion. In mice challenged intraperitoneally with live or killed mycobacteria, NOD2-dependent immune responses depended on the presence of bacterial namH. Finally, N-glycolyl MDP was more efficacious than N-acetyl MDP at inducing ovalbumin-specific T cell immunity in a model of adjuvancy. Our findings indicate that N-glycolyl MDP has a greater NOD2-stimulating activity than N-acetyl MDP, consistent with the historical observation attributing exceptional immunogenic activity to the mycobacterial cell wall.

PMID: 19581406 [PubMed - as supplied by publisher]
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david.crichton



Joined: 02 May 2008
Posts: 83

PostPosted: Fri Jul 24, 2009 1:50 pm    Post subject: audio interview Reply with quote

Just came across a short audio interview with Dr. Behr explaining the study and its potential significance

Audio: http://assets.muhc.ca/audio/news/Behr-Microbacteria-Jul-2009.mp3

Same text as the link from above in the first post but include it to show where audio link comes from: http://www.mcgill.ca/newsroom/news/item/?item_id=107644


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