The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis

Sanjay Lala, Keertan Dheda, Jung Su Chang, Jim F. Huggett, Louise U. Kim, Margaret A. Johnson, Graham A W Rook, Satish Keshav, Alimuddin Zumla

Research output: Contribution to journalArticle

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Abstract

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-α 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. Conclusion: 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.

Original languageEnglish
Article number96
JournalBMC Infectious Diseases
Volume7
DOIs
Publication statusPublished - Aug 16 2007
Externally publishedYes

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Pulmonary Tuberculosis
Mycobacterium tuberculosis
Messenger RNA
Tuberculosis
Leukocytes
Alveolar Epithelial Cells
Mononuclear Leukocytes
Toll-Like Receptor 2
Toll-Like Receptor 4
Therapeutic Irrigation
Mutant Proteins
Real-Time Polymerase Chain Reaction
Therapeutics
Macrophages
Apoptosis
Antigens
Lung
Survival
Population

ASJC Scopus subject areas

  • Infectious Diseases

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The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis. / Lala, Sanjay; Dheda, Keertan; Chang, Jung Su; Huggett, Jim F.; Kim, Louise U.; Johnson, Margaret A.; Rook, Graham A W; Keshav, Satish; Zumla, Alimuddin.

In: BMC Infectious Diseases, Vol. 7, 96, 16.08.2007.

Research output: Contribution to journalArticle

Lala, Sanjay ; Dheda, Keertan ; Chang, Jung Su ; Huggett, Jim F. ; Kim, Louise U. ; Johnson, Margaret A. ; Rook, Graham A W ; Keshav, Satish ; Zumla, Alimuddin. / The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis. In: BMC Infectious Diseases. 2007 ; Vol. 7.
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