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

 

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dc.contributor.author Lala, Sanjay en_ZA
dc.contributor.author Dheda, Keertan en_ZA
dc.contributor.author Chang, Jung-Su en_ZA
dc.contributor.author Huggett, Jim en_ZA
dc.contributor.author Kim, Louise en_ZA
dc.contributor.author Johnson, Margaret en_ZA
dc.contributor.author Rook, Graham en_ZA
dc.contributor.author Keshav, Satish en_ZA
dc.contributor.author Zumla, Alimuddin en_ZA
dc.date.accessioned 2015-10-12T10:53:41Z
dc.date.available 2015-10-12T10:53:41Z
dc.date.issued 2007 en_ZA
dc.identifier.citation Lala, S., Dheda, K., Chang, J. S., Huggett, J. F., Kim, L. U., Johnson, M. A., ... & Zumla, A. (2007). The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis. BMC infectious diseases, 7(1), 96. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/14174
dc.identifier.uri http://dx.doi.org/10.1186/1471-2334-7-96
dc.description.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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Biomed Central Ltd en_ZA
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_ZA
dc.source BMC Infectious Diseases en_ZA
dc.source.uri http://www.biomedcentral.com/bmcinfectdis/ en_ZA
dc.subject.other Pulmonology en_ZA
dc.title The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis en_ZA
dc.type Journal Article en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Pulmonology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Lala, S., Dheda, K., Chang, J., Huggett, J., Kim, L., Johnson, M., ... Zumla, A. (2007). The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis. <i>BMC Infectious Diseases</i>, http://hdl.handle.net/11427/14174 en_ZA
dc.identifier.chicagocitation Lala, Sanjay, Keertan Dheda, Jung-Su Chang, Jim Huggett, Louise Kim, Margaret Johnson, Graham Rook, Satish Keshav, and Alimuddin Zumla "The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis." <i>BMC Infectious Diseases</i> (2007) http://hdl.handle.net/11427/14174 en_ZA
dc.identifier.vancouvercitation Lala S, Dheda K, Chang J, Huggett J, Kim L, Johnson M, et al. The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis. BMC Infectious Diseases. 2007; http://hdl.handle.net/11427/14174. en_ZA
dc.identifier.ris TY - Journal Article AU - Lala, Sanjay AU - Dheda, Keertan AU - Chang, Jung-Su AU - Huggett, Jim AU - Kim, Louise AU - Johnson, Margaret AU - Rook, Graham AU - Keshav, Satish AU - Zumla, Alimuddin AB - 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. DA - 2007 DB - OpenUCT DO - 10.1186/1471-2334-7-96 DP - University of Cape Town J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2007 T1 - The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis TI - The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis UR - http://hdl.handle.net/11427/14174 ER - en_ZA


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