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Title: Expression of inhibitory regulators of innate immunity in patients with active tuberculosis
Authors: Dana C. Blok
Liesbeth M. Kager
Arie J. Hoogendijk
Ivar O. Lede
Wahid Rahman
Rumana Afroz
Paul Bresser
Jaring S. van der Zee
Aniruddha Ghose
Caroline E. Visser
Menno D. de Jong
Abu Shahed Md Zahed
Md Anwar Husain
Khan Mashrequl Alam
Pravat Chandra Barua
Mahtabuddin Hassan
Ahmed Hossain
Md Abu Tayab
Rene Lutter
Nick Day
Arjen M. Dondorp
Alex F. de Vos
Cornelis van 't Veer
Tom van der Poll
Academic Medical Centre, University of Amsterdam
Our Lady Hospital - Amsterdam
Chittagong Medical College Hospital
National TB Control Programme
Chest Disease Clinic Chittagong (CDCC)
Chittagong General Hospital
Mahidol University
Keywords: Medicine
Issue Date: 12-Dec-2015
Citation: BMC Infectious Diseases. Vol.15, No.1 (2015)
Abstract: © 2015 Blok et al.; licensee BioMed Central. Background: Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. Toll-like-receptors (TLRs) are important for the recognition of the causative agent Mycobacterium tuberculosis. Negative regulation of TLRs is necessary to control deleterious inflammatory damage, but could provide a means of immune evasion by M. tuberculosis as well. Methods: To obtain insight in the extent of expression of inhibitory regulators of immunity in patients with active TB, peripheral-blood-mononuclear-cells (PBMCs) and plasma were obtained from 54 TB patients and 29 healthy blood donors from Chittagong, Bangladesh. Bilateral alveolar macrophages were obtained from an infected versus a contralateral normal lung segment of 9 patients. Statistical analyses were performed using Mann-Whitney U and Wilcoxon matched pairs testing. Correlations were calculated using the Spearman rho test. Results: PBMCs harvested from TB patients demonstrated increased mRNA expression of IL-1-receptor-associated-kinase-M, suppressor-of-cytokine-signalling-3 and Toll-interacting-protein. Flow cytometry revealed enhanced expression of IL-1-receptor-like-1 (ST2) on lymphocytes. Plasma soluble ST2 was elevated in patients with TB and correlated with established TB biomarkers, most strongly with soluble interleukin-2 receptor subunit aα and interleukin-8. Alveolar macrophage mRNA expression of negative TLR regulators did not differ between the infected and contralateral lung side. Conclusion: These results show enhanced expression of distinct negative regulators of innate immunity in PBMCs of patients with TB and identify plasma soluble ST2 as a potential novel biomarker for TB disease activity.
ISSN: 14712334
Appears in Collections:Scopus 2011-2015

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