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NOD2 deficiency results in increased susceptibility to peptidoglycan-induced uveitis in mice.

Authors: Rosenzweig, HL  Galster, K  Vance, EE  Ensign-Lewis, J  Nunez, G  Davey, MP  Rosenbaum, JT 
Citation: Rosenzweig HL, etal., Invest Ophthalmol Vis Sci. 2011 Jun 9;52(7):4106-12. Print 2011 Jun.
Pubmed: (View Article at PubMed) PMID:21296813
DOI: Full-text: DOI:10.1167/iovs.10-6263

PURPOSE: The innate immune receptor NOD2 is a genetic cause of uveitis (Blau syndrome). Intriguingly, in the intestine where polymorphisms of NOD2 predispose to Crohn's disease, NOD2 reportedly suppresses inflammation triggered by the bacterial cell wall component, peptidoglycan (PGN). Whether NOD2 exerts a similar capacity in the regulation of ocular inflammation to PGN has not been explored. METHODS: NOD2, NOD1, or MyD88 knockout (KO) mice and their wild-type (WT) controls were administered an intravitreal injection of PGN (a metabolite of which is the NOD2 agonist, muramyl dipeptide), or synthetic TLR2/1 and TLR2/6 agonists, PamCSK4 and FSL-1. Ocular inflammation was assessed by intravital microscopy and histopathology. Cytokine production in eye tissue homogenates was measured by ELISA. RESULTS: PGN triggered uveitis in mice. This inflammation was abolished in the absence of the TLR signaling mediator MyD88. NOD2 exerted a negative regulatory role because PGN-triggered eye inflammation was exacerbated in NOD2 KO mice. Increased intravascular response coincided with enhanced leukocytes within the aqueous and vitreous humors. The enhanced susceptibility of NOD2 KO mice to PGN uveitis coincided with increased cytokine production of IL-12p40, IL-17, and IL-23 but not IL-12p70, TNFalpha, or IFNgamma. NOD1 deficiency did not result in the same sensitivity to PGN. Ocular inflammation induced by synthetic TLR2 agonists required MyD88 but not NOD2 or NOD1. CONCLUSIONS: NOD2 may serve differential roles in the eye to promote inflammation while also tempering cell responses to PGN akin to what has been reported in colitis.


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RGD Object Information
RGD ID: 5508729
Created: 2011-10-20
Species: All species
Last Modified: 2011-10-20
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.