NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis.

Abstract:

:Infection with Mycobacterium tuberculosis is one of the leading causes of death worldwide. Recognition of M. tuberculosis by pattern recognition receptors is crucial for activation of both innate and adaptive immune responses. In the present study, we demonstrate that nucleotide-binding oligomerization domain 2 (NOD2) and Toll-like receptors (TLRs) are two nonredundant recognition mechanisms of M. tuberculosis. CHO cell lines transfected with human TLR2 or TLR4 were responsive to M. tuberculosis. TLR2 knock-out mice displayed more than 50% defective cytokine production after stimulation with mycobacteria, whereas TLR4-defective mice also released 30% less cytokines compared to controls. Similarly, HEK293T cells transfected with NOD2 responded to stimulation with M. tuberculosis. The important role of NOD2 for the recognition of M. tuberculosis was demonstrated in mononuclear cells of individuals homozygous for the 3020insC NOD2 mutation, who showed an 80% defective cytokine response after stimulation with M. tuberculosis. Finally, the mycobacterial TLR2 ligand 19-kDa lipoprotein and the NOD2 ligand muramyl dipeptide synergized for the induction of cytokines, and this synergism was lost in cells defective in either TLR2 or NOD2. Together, these results demonstrate that NOD2 and TLR pathways are nonredundant recognition mechanisms of M. tuberculosis that synergize for the induction of proinflammatory cytokines.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Ferwerda G,Girardin SE,Kullberg BJ,Le Bourhis L,de Jong DJ,Langenberg DM,van Crevel R,Adema GJ,Ottenhoff TH,Van der Meer JW,Netea MG

doi

10.1371/journal.ppat.0010034

keywords:

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

279-85

issue

3

eissn

1553-7366

issn

1553-7374

journal_volume

1

pub_type

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