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 α and interleukin-8. Alveolar macrophage mRNA expression of negative TLR regulators did not differ between the infected and contralateral lung side.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. d.c.blok@amc.uva.nl.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. d.c.blok@amc.uva.nl.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Blok
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. L.M.Kager@amc.uva.nl.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. L.M.Kager@amc.uva.nl.
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Kager
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. A.J.Hoogendijk@amc.uva.nl.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. A.J.Hoogendijk@amc.uva.nl.
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. I.O.Lede@amc.uva.nl.|Department of Microbiology, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. I.O.Lede@amc.uva.nl.
authors.forename: Ivar O
authors.initials: IO
authors.lastname: Lede
authors.affiliation: Department of Internal Medicine, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. Wahid.Rahman001@yahoo.com.
authors.forename: Wahid
authors.initials: W
authors.lastname: Rahman
authors.affiliation: Department of Internal Medicine, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. drashika82@yahoo.com.
authors.forename: Rumana
authors.initials: R
authors.lastname: Afroz
authors.affiliation: Department of Pulmonology, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. P.Bresser@olvg.nl.|Department of Pulmonology, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. P.Bresser@olvg.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Bresser
authors.affiliation: Department of Pulmonology, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. j.s.vanderzee@amc.uva.nl.|Department of Pulmonology, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. j.s.vanderzee@amc.uva.nl.
authors.forename: Jaring S
authors.initials: JS
authors.lastname: van der Zee
authors.affiliation: Department of Internal Medicine, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. anrdghs@yahoo.com.
authors.forename: Aniruddha
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authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. C.E.Visser@amc.uva.nl.|Department of Microbiology, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. C.E.Visser@amc.uva.nl.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Visser
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. M.D.dejong@amc.uva.nl.|Department of Microbiology, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. M.D.dejong@amc.uva.nl.
authors.forename: Menno D
authors.initials: MD
authors.lastname: de Jong
authors.affiliation: Department of Internal Medicine, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. AbuSZahed@yahoo.com.
authors.forename: Abu Shahed Md
authors.initials: AS
authors.lastname: Zahed
authors.affiliation: Department of Microbiology, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. MdAHusain@hotmail.com.
authors.forename: Md Anwar
authors.initials: MA
authors.lastname: Husain
authors.affiliation: Department of Microbiology, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. KhMAlam@yahoo.com.
authors.forename: Khan Mashrequl
authors.initials: KM
authors.lastname: Alam
authors.affiliation: National TB Control and Leprosy Elimination Program, Dhaka, Bangladesh. PravatBarua@yahoo.com.
authors.forename: Pravat Chandra
authors.initials: PC
authors.lastname: Barua
authors.affiliation: Department of Internal Medicine, Chittagong Medical College and Hospital (CMCH), Chittagong, Bangladesh. MahtabH@yahoo.com.
authors.forename: Mahtabuddin
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authors.lastname: Hassan
authors.affiliation: Chest Disease Clinic Chittagong (CDCC), Chittagong, Bangladesh.
authors.forename: Ahmed
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authors.affiliation: Chittagong General Hospital, Chittagong, Bangladesh. ATayab@google.com.
authors.forename: Md Abu
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authors.affiliation: Department of Pulmonology, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. R.lutter@amc.uva.nl.|Department of Experimental Immunology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. R.lutter@amc.uva.nl.
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Mahidol Oxford Tropical Research Unit, Mahidol University, Bangkok, Thailand. nickd@tropmedres.ac.
authors.forename: Nick
authors.initials: N
authors.lastname: Day
authors.affiliation: Mahidol Oxford Tropical Research Unit, Mahidol University, Bangkok, Thailand. arjen@tropmedres.ac.
authors.forename: Arjen M
authors.initials: AM
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authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. a.f.devos@amc.uva.nl.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. a.f.devos@amc.uva.nl.
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. c.vantveer@amc.uva.nl.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. c.vantveer@amc.uva.nl.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. t.vanderpoll@amc.uva.nl.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. t.vanderpoll@amc.uva.nl.|Division of Infectious Diseases, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands. t.vanderpoll@amc.uva.nl.
authors.forename: Tom
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mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001459:Bangladesh / Q000453:epidemiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D051193:Toll-Like Receptors