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

Lala, S; Dheda, K; Chang, JS; Huggett, JF; Kim, LU; Johnson, MA; Rook, GAW; ... Zumla, A; + view all (2007) The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis. BMC Infectious Diseases , 7 , Article 96. 10.1186/1471-2334-7-96. Green open access

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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-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.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.

Type: Article
Title: The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1471-2334-7-96
Publisher version: http://dx.doi.org/10.1186/1471-2334-7-96
Language: English
Additional information: © 2007 Lala et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: INTESTINAL EPITHELIAL-CELLS, TOLL-LIKE RECEPTORS, MYCOBACTERIUM-TUBERCULOSIS, CROHNS-DISEASE, IN-VITRO, KAPPA-B, INFECTION, SUSCEPTIBILITY, GENE, IL-4-DELTA-2
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/165467
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