International Journal of Medical Sciences

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18 October 2017

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Int J Med Sci 2013; 10(8):1003-1014. doi:10.7150/ijms.6437

Research Paper

Potential Function of Granulysin, Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

Nada Pitabut1, Shinsaku Sakurada2, Takahiro Tanaka2, Chutharut Ridruechai1, Junko Tanuma3, Takahiro Aoki3, Pacharee Kantipong4, Surachai Piyaworawong5, Nobuyuki Kobayashi6, Panadda Dhepakson7, Hideki Yanai8, Norio Yamada9, Shinichi Oka3, Masaji Okada10, Srisin Khusmith1,✉, Naoto Keicho2

1. Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
2. Department of Respiratory Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan;
3. AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan;
4. Department of Medicine, Chiang Rai Regional Hospital, Chiang Rai, Thailand;
5. Mae Chang District Hospital, Chiang Rai, Thailand;
6. Department of Pulmonary Medicine, Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan;
7. Medical Biotechnology Center, National Institute of Health, Department of Medical Science, Ministry of Public Health, Nonthaburi, Thailand;
8. TB/HIV Research Project, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Chiang Rai, Thailand;
9. Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Tokyo, Japan;
10. Clinical Research Center, National Hospital Organization, Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan.

Abstract

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy.

Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9+Vδ2+ T cells, CD4+ T cells and CD8+ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection.

Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry.

Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8+ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed.

Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection.

Keywords: Granulysin, TB, HIV, HIV/TB Coinfection, Lymphocytes Subsets.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Pitabut N, Sakurada S, Tanaka T, Ridruechai C, Tanuma J, Aoki T, Kantipong P, Piyaworawong S, Kobayashi N, Dhepakson P, Yanai H, Yamada N, Oka S, Okada M, Khusmith S, Keicho N. Potential Function of Granulysin, Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection. Int J Med Sci 2013; 10(8):1003-1014. doi:10.7150/ijms.6437. Available from http://www.medsci.org/v10p1003.htm