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World J Virology. Feb 12, 2015; 4(1): 17-24
Published online Feb 12, 2015. doi: 10.5501/wjv.v4.i1.17
Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection
Esaki M Shankar, Vijayakumar Velu, Adeeba Kamarulzaman, Marie Larsson
Esaki M Shankar, Tropical Infectious Disease Research and Education Center, Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia
Vijayakumar Velu, Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, United States
Adeeba Kamarulzaman, Center of Excellence for Research in AIDS, University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia
Marie Larsson, Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden
Author contributions: Shankar EM designed research; Shankar EM and Velu V performed research; Kamarulzaman A and Larsson M contributed new reagents or analytic tools; Shankar EM and Velu V analyzed data; Shankar EM and Velu V wrote the paper.
Supported by a grant from the University of Malaya Research Grant RG448-12HTM of the Health and Translational Medicine Research Cluster to Esaki M Shankar; and UM.C/625/1/HIR/MoHE/MED/014 to Adeeba Kamarulzaman by the High Impact Research (HIR); University of Malaya, SIDA SARC, VINNMER for Vinnova, Linköping University Hospital Research Fund, CALF and the Swedish Society of Medicine; and the Swedish International Development Cooperation Agency, the Swedish Physicians against AIDS Research Foundation, the Swedish Research Council, Marie Larsson, No. AI52731.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Esaki M Shankar, Associate professor, Tropical Infectious Disease Research and Education Center, Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia. shankarem@um.edu.my
Telephone: +60-3-79492755
Received: August 4, 2014
Peer-review started: August 6, 2014
First decision: September 16, 2014
Revised: September 30, 2014
Accepted: October 23, 2014
Article in press: October 27, 2014
Published online: February 12, 2015
Processing time: 169 Days and 4 Hours
Core Tip

Core tip: The mechanistic aspects associated with increased expression of senescence and immune activa-tion markers cluster of differentiation (CD) 38, CD69, CD57, human leukocyte antigen-DR, and the down-regulation of functional molecules, viz., CD28, CD27, CD40L and CD127 on human immunodeficiency virus-specific T cells appear to be crucial in the immunopathogenesis of HIV-tuberculosis (HIV-TB) co-infection. Mycobacterium tuberculosis appears to play a major role in accelerating HIV disease progression, by directly or indirectly facilitating factors associated with immune senescence. Measures to ameliorate immunosenescence and immune activation appear to stem from identification of novel targets of downstream senescence signaling. Restoration of molecules associated with T-cell homeostasis, differentiation, cell survival and proliferation abilities of HIV-specific CD8+ T cells is key to foster functional immune responses.