title: Increased intra- and extracellular granzyme expression in patients with tuberculosis.
abstract: Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. Granzymes (gzms) are proteases mainly found in cytotoxic lymphocytes, but also extracellularly. While the role of gzms in target cell death has been widely characterized, considerable evidence points towards broader roles related to infectious and inflammatory responses. To investigate the expression of the gzms in TB, intracellular gzms A, B and K were measured by flow cytometry in lymphocyte populations from peripheral blood mononuclear cells from 18 TB patients and 12 healthy donors from Bangladesh, and extracellular levels of gzmA and B were measured in serum from 58 TB patients and 31 healthy controls. TB patients showed increased expression of gzmA in CD8(+) T, CD4(+) T and CD56(+) T, but not NK, cells, and of gzmB in CD8(+) T cells, when compared to controls. GzmK expression was not altered in TB patients in any lymphocyte subset. The extracellular levels of gzmA and, to a lesser extent, of gzmB, were increased in TB patients, but did not correlate with intracellular gzm expression in lymphocyte subsets. Our results reveal enhanced intra- and extracellular expression of gzmA and B in patients with pulmonary TB, suggesting that gzms are part of the host response to tuberculosis.
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: ihalemgl@yahoo.es.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Garcia-Laorden
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: 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, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: 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, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: a.j.hoogendijk@amc.uva.nl.
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.affiliation: Department of Immunopathology, Sanquin Research, Plesmanlaan 125, 1066CX Amsterdam, The Netherlands. Electronic address: g.vanmierlo@sanquin.nl.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: van Mierlo
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Department of Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: 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 & Hospital (CMCH), Chittagong, Bangladesh. Electronic address: wahid.rahman001@yahoo.com.
authors.forename: Wahid
authors.initials: W
authors.lastname: Rahman
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh. Electronic address: drashika82@yahoo.com.
authors.forename: Rumana
authors.initials: R
authors.lastname: Afroz
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh. Electronic address: anrdghs@yahoo.com.
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Ghose
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Department of Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: c.e.visser@amc.uva.nl.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Visser
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Abu Shahed
authors.initials: AS
authors.lastname: Md Zahed
authors.affiliation: Department of Microbiology, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Md Anwar
authors.initials: MA
authors.lastname: Husain
authors.affiliation: Department of Microbiology, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Khan Mashrequl
authors.initials: KM
authors.lastname: Alam
authors.affiliation: National TB Control & Leprosy Elimination Program, Dhaka, Bangladesh.
authors.forename: Pravat
authors.initials: P
authors.lastname: Chandra Barua
authors.affiliation: Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh.
authors.forename: Mahtabuddin
authors.initials: M
authors.lastname: Hassan
authors.affiliation: Chest Disease Clinic Chittagong (CDCC), Anderkilla, Chittagong, Bangladesh.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hossain
authors.affiliation: Chittagong General Hospital, Arderkilla, Chittagong, Bangladesh.
authors.forename: Md Abu
authors.initials: MA
authors.lastname: Tayab
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 3/F 60th Anniversary Chalermprakiat Building, 420/6 Rajvithi Road, 10400 Bangkok, Thailand. Electronic address: nickd@tropmedres.ac.
authors.forename: Nick
authors.initials: N
authors.lastname: Day
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 3/F 60th Anniversary Chalermprakiat Building, 420/6 Rajvithi Road, 10400 Bangkok, Thailand. Electronic address: arjen@tropmedres.ac.
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: 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, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: t.vanderpoll@amc.uva.nl.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000328:Adult; D001459:Bangladesh; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000097:blood*; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; C509213:GZMB protein, human; C088546:GZMK protein, human; D053804:Granzymes; C509212:GZMA protein, human
keywords: Cytokines; Granzymes; T lymphocytes; Tuberculosis