The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis.
BACKGROUND
NOD2, an intracellular pathogen recognition sensor, modulates innate defences to muropeptides derived from various bacterial species, including Mycobacterium tuberculosis (MTB). Experimentally, NOD2 attenuates two key putative mycobactericidal mechanisms. TNF-alpha synthesis is markedly reduced in MTB-antigen stimulated-mononuclear cells expressing mutant NOD2 proteins. NOD2 agonists also induce resistance to apoptosis, and may thus facilitate the survival of MTB in infected macrophages. To further define a role for NOD2 in disease pathogenesis, we analysed NOD2 transcriptional responses in pulmonary leucocytes and mononuclear cells harvested from patients with pulmonary tuberculosis (PTB).


METHODS
We analysed NOD2 mRNA expression by real-time polymerase chain-reaction in alveolar lavage cells obtained from 15 patients with pulmonary tuberculosis and their matched controls. We compared NOD2 transcriptional responses, in peripheral leucocytes, before and after anti-tuberculous treatment in 10 patients. In vitro, we measured NOD2 mRNA levels in MTB-antigen stimulated-mononuclear cells.


RESULTS
No significant differences in NOD2 transcriptional responses were detected in patients and controls. In some patients, however, NOD2 expression was markedly increased and correlated with toll-like-receptor 2 and 4 expression. In whole blood, NOD2 mRNA levels increased significantly after completion of anti-tuberculosis treatment. NOD2 expression levels did not change significantly in mononuclear cells stimulated with mycobacterial antigens in vitro.


CONCLUSIONS
There are no characteristic NOD2 transcriptional responses in PTB. Nonetheless, the increased levels of NOD2 expression in some patients with severe tuberculosis, and the increases in expression levels within peripheral leucocytes following treatment merit further studies in selected patient and control populations.
Lala
Sanjay
S
Centre for Gastroenterology, Royal Free and University College Medical School & Royal Free Hospital NHS Trust, London, UK. s.lala@mweb.co.za
Dheda
Keertan
K
Chang
Jung-Su
JS
Huggett
Jim F
JF
Kim
Louise U
LU
Johnson
Margaret A
MA
Rook
Graham A W
GA
Keshav
Satish
S
Zumla
Alimuddin
A
D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4
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