%0 Journal Article
%@ 1537-6613
%A Chodisetti, Sathi Babu
%A Gowthaman, Uthaman
%A Rai, Pradeep K
%A Vidyarthi, Aurobind
%A Khan, Nargis
%A Agrewala, J N
%D 2015
%F open:1653
%I Oxford University Press
%J The Journal of infectious diseases
%K LR-2; Th1 cells; chronic infection; exhaustion markers; tuberculosis
%N 3
%P 486-96
%T Triggering through Toll-like receptor 2 limits chronically stimulated T-helper type 1 cells from undergoing exhaustion.
%U http://crdd.osdd.net/open/1653/
%V 211
%X 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.
%Z Copyright of this article belongs to Oxford University Press