Triggering through Toll-like receptor 2 limits chronically stimulated T-helper type 1 cells from undergoing exhaustion.

Chodisetti, Sathi Babu and Gowthaman, Uthaman and Rai, Pradeep K and Vidyarthi, Aurobind and Khan, Nargis and Agrewala, J N (2015) Triggering through Toll-like receptor 2 limits chronically stimulated T-helper type 1 cells from undergoing exhaustion. The Journal of infectious diseases, 211 (3). pp. 486-96. ISSN 1537-6613

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Abstract

Chronic infections result in T-cell exhaustion, a state of functional unresponsiveness. To control the infection, it is important to salvage the exhausted T cells. In this study, we delivered signals through Toll-like receptor 2 (TLR-2) to reinvigorate functionality in chronically activated T-helper type 1 (Th1) cells. This process significantly augmented the expression of T-bet, interferon γ, interleukin 2, and the antiapoptotic molecule Bcl-2, whereas it dampened the display of the exhaustion markers programmed death receptor 1 (PD-1) and lymphocyte activation gene 3 (Lag-3). Additionally, TLR-2 signaling bolstered the ability of chronically stimulated Th1 cells to activate B cells. Finally, the results were substantiated by observing reduced lung pathology upon administration of TLR-2 agonist in the chronic infection model of tuberculosis. These data demonstrated the importance of TLR-2 in rescuing chronically activated Th1 cells from undergoing exhaustion. This study will pave a way for targeting TLR-2 in developing therapeutic strategies to treat chronic diseases involving loss of Th1 cell function.

Item Type:	Article
Additional Information:	Copyright of this article belongs to Oxford University Press
Uncontrolled Keywords:	LR-2; Th1 cells; chronic infection; exhaustion markers; tuberculosis
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	13 Jul 2015 10:35
Last Modified:	22 Jul 2015 04:21
URI:	http://crdd.osdd.net/open/id/eprint/1653

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