TY - JOUR KW - TB KW - Morbidity KW - GZMS KW - Granzymes KW - Cytokines AU - Garcia-Laorden IM AU - Blok D AU - Kager LM AU - Hoogendijk A AU - Mierlo G AU - Lede I AU - Rahman W AU - Afroz R AU - Ghose A AU - Visser CE AU - Md Zahed AS AU - Husain MA AU - Alam KM AU - Chandra Barua P AU - Hassan M AU - Hossain A AU - Tayab MA AU - Day N AU - Dondorp AM AU - Vos AF AU - Poll T 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.

BT - Tuberculosis (Edinburgh, Scotland) C1 -

http://www.ncbi.nlm.nih.gov/pubmed/26156785?dopt=Abstract

DO - 10.1016/j.tube.2015.05.016 IS - Jun 20 J2 - Tuberculosis (Edinb) LA - eng 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.

PY - 2015 EP - [Epub ahead of print] T2 - Tuberculosis (Edinburgh, Scotland) TI - Increased intra- and extracellular granzyme expression in patients with tuberculosis. SN - 1873-281X ER -