Expression of inhibitory regulators of innate immunity in patients with active tuberculosis

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

doi:https://doi.org/10.1186/s12879-015-0833-z

Expression of inhibitory regulators of innate immunity in patients with active tuberculosis

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 DayArjen M. Dondorp, Alex F. de Vos, Cornelis van 't Veer, Tom van der Poll

Research output: Contribution to journal › Article › Academic › peer-review

8 Citations (Scopus)

Abstract

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 a 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

Original language	English
Pages (from-to)	98
Journal	BMC Infectious Diseases
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s12879-015-0833-z
Publication status	Published - 2015

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Blok, D. C., Kager, L. M., Hoogendijk, A. J., Lede, I. O., Rahman, W., Afroz, R., Bresser, P., van der Zee, J. S., Ghose, A., Visser, C. E., de Jong, M. D., Zahed, A. S. M., Husain, M. A., Alam, K. M., Barua, P. C., Hassan, M., Hossain, A., Tayab, M. A., Lutter, R., ... van der Poll, T. (2015). Expression of inhibitory regulators of innate immunity in patients with active tuberculosis. BMC Infectious Diseases, 15(1), 98. https://doi.org/10.1186/s12879-015-0833-z

@article{9a25538b2f304a73bdcb6cad1a7f9b46,

title = "Expression of inhibitory regulators of innate immunity in patients with active tuberculosis",

abstract = "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 a 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",

author = "Blok, {Dana C.} and Kager, {Liesbeth M.} and Hoogendijk, {Arie J.} and Lede, {Ivar O.} and Wahid Rahman and Rumana Afroz and Paul Bresser and {van der Zee}, {Jaring S.} and Aniruddha Ghose and Visser, {Caroline E.} and {de Jong}, {Menno D.} and Zahed, {Abu Shahed Md} and Husain, {Md Anwar} and Alam, {Khan Mashrequl} and Barua, {Pravat Chandra} and Mahtabuddin Hassan and Ahmed Hossain and Tayab, {Md Abu} and Rene Lutter and Nick Day and Dondorp, {Arjen M.} and {de Vos}, {Alex F.} and {van 't Veer}, Cornelis and {van der Poll}, Tom",

year = "2015",

doi = "https://doi.org/10.1186/s12879-015-0833-z",

language = "English",

volume = "15",

pages = "98",

journal = "BMC Infectious Diseases",

issn = "1471-2334",

publisher = "BioMed Central",

number = "1",

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Blok, DC, Kager, LM, Hoogendijk, AJ, Lede, IO, Rahman, W, Afroz, R, Bresser, P, van der Zee, JS, Ghose, A, Visser, CE , de Jong, MD, Zahed, ASM, Husain, MA, Alam, KM, Barua, PC, Hassan, M, Hossain, A, Tayab, MA, Lutter, R, Day, N, Dondorp, AM, de Vos, AF , van 't Veer, C & van der Poll, T 2015, 'Expression of inhibitory regulators of innate immunity in patients with active tuberculosis', BMC Infectious Diseases, vol. 15, no. 1, pp. 98. https://doi.org/10.1186/s12879-015-0833-z

TY - JOUR

T1 - Expression of inhibitory regulators of innate immunity in patients with active tuberculosis

AU - Blok, Dana C.

AU - Kager, Liesbeth M.

AU - Hoogendijk, Arie J.

AU - Lede, Ivar O.

AU - Rahman, Wahid

AU - Afroz, Rumana

AU - Bresser, Paul

AU - van der Zee, Jaring S.

AU - Ghose, Aniruddha

AU - Visser, Caroline E.

AU - de Jong, Menno D.

AU - Zahed, Abu Shahed Md

AU - Husain, Md Anwar

AU - Alam, Khan Mashrequl

AU - Barua, Pravat Chandra

AU - Hassan, Mahtabuddin

AU - Hossain, Ahmed

AU - Tayab, Md Abu

AU - Lutter, Rene

AU - Day, Nick

AU - Dondorp, Arjen M.

AU - de Vos, Alex F.

AU - van 't Veer, Cornelis

AU - van der Poll, Tom

PY - 2015

Y1 - 2015

N2 - 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 a 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

AB - 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 a 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

U2 - https://doi.org/10.1186/s12879-015-0833-z

DO - https://doi.org/10.1186/s12879-015-0833-z

M3 - Article

C2 - 25887604

SN - 1471-2334

VL - 15

SP - 98

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

IS - 1

ER -