Expression of <it>M</it>. <it>tuberculosis</it>-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis
<p>Abstract</p> <p>Background</p> <p>Appropriate immune activation of T cells and macrophages is central for the control of <it>Mycobacterium tuberculosis</it> infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppr...
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| Format: | Article |
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BMC
2013-01-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | http://www.biomedcentral.com/1471-2334/13/13 |
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| author | Masood Kiran I Rottenberg Martin E Salahuddin Naseem Irfan Muhammad Rao Nisar Carow Berit Islam Muniba Hussain Rabia Hasan Zahra |
| author_facet | Masood Kiran I Rottenberg Martin E Salahuddin Naseem Irfan Muhammad Rao Nisar Carow Berit Islam Muniba Hussain Rabia Hasan Zahra |
| author_sort | Masood Kiran I |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Appropriate immune activation of T cells and macrophages is central for the control of <it>Mycobacterium tuberculosis</it> infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules – 1 and 3 and CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMCs) were isolated from patients with pulmonary TB (PTB, n = 33), extra-pulmonary TB (ETB, n = 33) and healthy endemic controls (EC, n = 15). Cases were classified as moderately advanced or far advanced PTB, and less severe or severe disseminated ETB. <it>M</it>. <it>tuberculosis</it> -stimulated IFN-γ, SOCS1, SOCS3 and FoxP3 gene expression and secretion of Th1 and Th2 cytokines was measured. Statistical analysis was performed using Mann–Whitney U, Wilcoxon Rank and Kruskal Wallis non-parametric tests.</p> <p>Results</p> <p>In un-stimulated PBMCs, IL-6 (p = 0.018) and IL-10 (p = 0.013) secretion levels were increased in PTB while IL-10 was also increased in ETB (p = 0.003), all in comparison with EC. <it>M</it>. <it>tuberculosis</it>-stimulated IL-6 (p = 0.003) was lowered in ETB as compared with EC. SOCS1 mRNA expression in <it>M</it>. <it>tuberculosis</it> stimulated PBMCs levels in moderately advanced PTB (p = 0.022), far advanced (p = 0.014) PTB, and severe ETB (p = 0.009) were raised as compared with EC. On the other hand, SOCS1 mRNA titers were reduced in less severe ETB, in comparison with severe ETB (p = 0.027) and far advanced PTB (p = 0.016). SOCS3 mRNA accumulation was reduced in far advanced PTB (p = 0.007) and FoxP3 mRNA expression was increased in less severe ETB as compared with EC (p = 0.017).</p> <p>Conclusions</p> <p>The lowered SOCS1 mRNA levels in patients with less severe extra-pulmonary TB as compared to those with more severe ETB and PTB may lead to elevated IFN-γ pathway gene expression in the latter group. As localized ETB has shown to be associated with more effective Th1 immunity and adaptive responses, this suggests a role for SOCS1 in determining disease outcome in extra-pulmonary TB.</p> |
| first_indexed | 2024-12-18T05:14:44Z |
| format | Article |
| id | doaj.art-ff615bd8bb554acd9b91997c871f6f3f |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-18T05:14:44Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-ff615bd8bb554acd9b91997c871f6f3f2022-12-21T21:19:48ZengBMCBMC Infectious Diseases1471-23342013-01-011311310.1186/1471-2334-13-13Expression of <it>M</it>. <it>tuberculosis</it>-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosisMasood Kiran IRottenberg Martin ESalahuddin NaseemIrfan MuhammadRao NisarCarow BeritIslam MunibaHussain RabiaHasan Zahra<p>Abstract</p> <p>Background</p> <p>Appropriate immune activation of T cells and macrophages is central for the control of <it>Mycobacterium tuberculosis</it> infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules – 1 and 3 and CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMCs) were isolated from patients with pulmonary TB (PTB, n = 33), extra-pulmonary TB (ETB, n = 33) and healthy endemic controls (EC, n = 15). Cases were classified as moderately advanced or far advanced PTB, and less severe or severe disseminated ETB. <it>M</it>. <it>tuberculosis</it> -stimulated IFN-γ, SOCS1, SOCS3 and FoxP3 gene expression and secretion of Th1 and Th2 cytokines was measured. Statistical analysis was performed using Mann–Whitney U, Wilcoxon Rank and Kruskal Wallis non-parametric tests.</p> <p>Results</p> <p>In un-stimulated PBMCs, IL-6 (p = 0.018) and IL-10 (p = 0.013) secretion levels were increased in PTB while IL-10 was also increased in ETB (p = 0.003), all in comparison with EC. <it>M</it>. <it>tuberculosis</it>-stimulated IL-6 (p = 0.003) was lowered in ETB as compared with EC. SOCS1 mRNA expression in <it>M</it>. <it>tuberculosis</it> stimulated PBMCs levels in moderately advanced PTB (p = 0.022), far advanced (p = 0.014) PTB, and severe ETB (p = 0.009) were raised as compared with EC. On the other hand, SOCS1 mRNA titers were reduced in less severe ETB, in comparison with severe ETB (p = 0.027) and far advanced PTB (p = 0.016). SOCS3 mRNA accumulation was reduced in far advanced PTB (p = 0.007) and FoxP3 mRNA expression was increased in less severe ETB as compared with EC (p = 0.017).</p> <p>Conclusions</p> <p>The lowered SOCS1 mRNA levels in patients with less severe extra-pulmonary TB as compared to those with more severe ETB and PTB may lead to elevated IFN-γ pathway gene expression in the latter group. As localized ETB has shown to be associated with more effective Th1 immunity and adaptive responses, this suggests a role for SOCS1 in determining disease outcome in extra-pulmonary TB.</p>http://www.biomedcentral.com/1471-2334/13/13SOCS moleculesCytokine regulationTuberculosis |
| spellingShingle | Masood Kiran I Rottenberg Martin E Salahuddin Naseem Irfan Muhammad Rao Nisar Carow Berit Islam Muniba Hussain Rabia Hasan Zahra Expression of <it>M</it>. <it>tuberculosis</it>-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis BMC Infectious Diseases SOCS molecules Cytokine regulation Tuberculosis |
| title | Expression of <it>M</it>. <it>tuberculosis</it>-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis |
| title_full | Expression of <it>M</it>. <it>tuberculosis</it>-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis |
| title_fullStr | Expression of <it>M</it>. <it>tuberculosis</it>-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis |
| title_full_unstemmed | Expression of <it>M</it>. <it>tuberculosis</it>-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis |
| title_short | Expression of <it>M</it>. <it>tuberculosis</it>-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis |
| title_sort | expression of it m it it tuberculosis it induced suppressor of cytokine signaling socs 1 socs3 foxp3 and secretion of il 6 associates with differing clinical severity of tuberculosis |
| topic | SOCS molecules Cytokine regulation Tuberculosis |
| url | http://www.biomedcentral.com/1471-2334/13/13 |
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