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Open Access Highly Accessed Research article

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

Sanjay Lala1, Keertan Dheda23*, Jung-Su Chang2, Jim F Huggett2, Louise U Kim2, Margaret A Johnson4, Graham AW Rook2, Satish Keshav1 and Alimuddin Zumla2

Author Affiliations

1 Centre for Gastroenterology, Royal Free and University College Medical School & Royal Free Hospital NHS Trust, London, UK

2 Centre for Infectious Diseases and International Health, Royal Free Hospital NHS Trust, London, UK

3 Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology, University of Cape Town, South Africa

4 Dept. of Thoracic and HIV Medicine, Royal Free Hospital NHS Trust, London, UK

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BMC Infectious Diseases 2007, 7:96  doi:10.1186/1471-2334-7-96

Published: 16 August 2007

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.