title: Triggering through Toll-like receptor 2 limits chronically stimulated T-helper type 1 cells from undergoing exhaustion.
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.
authors.affiliation: Immunology Laboratory, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, India.
authors.forename: Sathi Babu
authors.initials: SB
authors.lastname: Chodisetti
authors.affiliation: Immunology Laboratory, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, India.
authors.forename: Uthaman
authors.initials: U
authors.lastname: Gowthaman
authors.affiliation: Immunology Laboratory, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, India.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Rai
authors.affiliation: Immunology Laboratory, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, India.
authors.forename: Aurobind
authors.initials: A
authors.lastname: Vidyarthi
authors.affiliation: Immunology Laboratory, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, India.
authors.forename: Nargis
authors.initials: N
authors.lastname: Khan
authors.affiliation: Immunology Laboratory, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh, India.
authors.forename: Javed N
authors.initials: JN
authors.lastname: Agrewala
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D007376:Interleukin-2; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D019253:Proto-Oncogene Proteins c-bcl-2; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse
keywords: TLR-2; Th1 cells; chronic infection; exhaustion markers; tuberculosis