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

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dc.contributor.authorLala, Sanjayen_ZA
dc.contributor.authorDheda, Keertanen_ZA
dc.contributor.authorChang, Jung-Suen_ZA
dc.contributor.authorHuggett, Jimen_ZA
dc.contributor.authorKim, Louiseen_ZA
dc.contributor.authorJohnson, Margareten_ZA
dc.contributor.authorRook, Grahamen_ZA
dc.contributor.authorKeshav, Satishen_ZA
dc.contributor.authorZumla, Alimuddinen_ZA
dc.date.accessioned2015-10-12T10:53:41Z
dc.date.available2015-10-12T10:53:41Z
dc.date.issued2007en_ZA
dc.description.abstractBACKGROUND: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.identifier.apacitationLala, 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/11427/14174en_ZA
dc.identifier.chicagocitationLala, 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/11427/14174en_ZA
dc.identifier.citationLala, 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.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
dc.identifier.urihttp://hdl.handle.net/11427/14174
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2334-7-96
dc.identifier.vancouvercitationLala 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.language.isoengen_ZA
dc.publisherBiomed Central Ltden_ZA
dc.publisher.departmentDivision of Pulmonologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Infectious Diseasesen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcinfectdis/en_ZA
dc.subject.otherPulmonologyen_ZA
dc.titleThe pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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