title: Triggering through Toll-like receptor 2 limits chronically stimulated T-helper type 1 cells from undergoing exhaustion.
creator: Chodisetti, Sathi Babu
creator: Gowthaman, Uthaman
creator: Rai, Pradeep K
creator: Vidyarthi, Aurobind
creator: Khan, Nargis
creator: Agrewala, J N
subject: QR Microbiology
description: 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.
publisher: Oxford University Press
date: 2015-02-01
type: Article
type: PeerReviewed
format: application/pdf
identifier: http://crdd.osdd.net/open/1653/1/JNA%20...%20J%20Infect%20Dis.-2015-Chodisetti-486-96.pdf
relation: http://jid.oxfordjournals.org/content/211/3/486.long
identifier:   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     
relation: http://crdd.osdd.net/open/1653/