TY - JOUR
T1 - Increased intra- and extracellular granzyme expression in patients with tuberculosis
AU - Garcia-Laorden, M. Isabel
AU - Blok, Dana C.
AU - Kager, Liesbeth M.
AU - Hoogendijk, Arie J.
AU - van Mierlo, Gerard J.
AU - Lede, Ivar O.
AU - Rahman, Wahid
AU - Afroz, Rumana
AU - Ghose, Aniruddha
AU - Visser, Caroline E.
AU - Md Zahed, Abu Shahed
AU - Husain, Md Anwar
AU - Alam, Khan Mashrequl
AU - Chandra Barua, Pravat
AU - Hassan, Mahtabuddin
AU - Hossain, Ahmed
AU - Tayab, Md Abu
AU - Day, Nick
AU - Dondorp, Arjen M.
AU - de Vos, Alex F.
AU - van der Poll, Tom
PY - 2015
Y1 - 2015
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.tube.2015.05.016
DO - https://doi.org/10.1016/j.tube.2015.05.016
M3 - Article
C2 - 26156785
SN - 1472-9792
VL - 95
SP - 575
EP - 580
JO - Tuberculosis (Edinburgh, Scotland)
JF - Tuberculosis (Edinburgh, Scotland)
IS - 5
ER -