Increased intra- and extracellular granzyme expression in patients with tuberculosis - 06/07/15

Doi : 10.1016/j.tube.2015.05.016

M. Isabel Garcia-Laorden ^a,^b,^⁎ , Dana C. Blok ^a,^b , Liesbeth M. Kager ^a,^b , Arie J. Hoogendijk ^a,^b , Gerard J. van Mierlo ^c , Ivar O. Lede ^a,^d , Wahid Rahman ^e , Rumana Afroz ^e , Aniruddha Ghose ^e , Caroline E. Visser ^a,^d , Abu Shahed Md Zahed ^e, Md Anwar Husain ^f, Khan Mashrequl Alam ^f, Pravat Chandra Barua ^g, Mahtabuddin Hassan ^e, Ahmed Hossain ^h,^{^{1
Dr. Hossain passed away during the course of the study.}}, Md Abu Tayab ⁱ, Nick Day ^j , Arjen M. Dondorp ^j , Alex F. de Vos ^a,^b , Tom van der Poll ^a,^b,^k
^a Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
^b Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
^c Department of Immunopathology, Sanquin Research, Plesmanlaan 125, 1066CX Amsterdam, The Netherlands
^d Department of Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
^e Department of Internal Medicine, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh
^f Department of Microbiology, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh
^g National TB Control & Leprosy Elimination Program, Dhaka, Bangladesh
^h Chest Disease Clinic Chittagong (CDCC), Anderkilla, Chittagong, Bangladesh
ⁱ Chittagong General Hospital, Arderkilla, Chittagong, Bangladesh
^j 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
^k Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

^∗Corresponding author. Academic Medical Center, Center for Experimental and Molecular Medicine, Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. Tel.: +31 20 5665910; fax: +31 20 6977192.

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Summary

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.

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Keywords : Tuberculosis, Granzymes, T lymphocytes, Cytokines