title: Toll-Like Receptor 2 Targeted Rectification of Impaired CD8⁺ T Cell Functions in Experimental Leishmania donovani Infection Reinstates Host Protection.
abstract: Leishmania donovani, a protozoan parasite, causes the disease visceral leishmanisis (VL), characterized by inappropriate CD8+ T-cell activation. Therefore, we examined whether the Toll-like Receptor 2 (TLR2) ligand Ara-LAM, a cell wall glycolipid from non-pathogenic Mycobacterium smegmatis, would restore CD8+ T-cell function during VL. We observed that by efficient upregulation of TLR2 signaling-mediated NF-κB translocation and MAPK signaling in CD8+ T-cells (CD25+CD28+IL-12R+IFN-γR+), Ara-LAM triggered signaling resulted in the activation of T-bet, which in turn, induced transcription favourable histone modification at the IFN-γ, perforin, granzyme-B promoter regions in CD8+ T-cells. Thus, we conclude that Ara-LAM induced efficient activation of effector CD8+ T-cells by upregulating the expression of IFN-γ, perforin and granzyme-B in an NF-κB and MAPK induced T-bet dependent manner in VL.
authors.affiliation: The Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Syamdas
authors.initials: S
authors.lastname: Bandyopadhyay
authors.affiliation: The Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Santanu
authors.initials: S
authors.lastname: Kar Mahapatra
authors.affiliation: The Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Bidisha
authors.initials: B
authors.lastname: Paul Chowdhury
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar Jha
authors.affiliation: The Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Shibali
authors.initials: S
authors.lastname: Das
authors.affiliation: The Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Kuntal
authors.initials: K
authors.lastname: Halder
authors.affiliation: The Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Suchandra
authors.initials: S
authors.lastname: Bhattacharyya Majumdar
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune, India.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Saha
authors.affiliation: The Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000469:parasitology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D053804:Granzymes / Q000235:genetics; D006657:Histones / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D017471:Receptors, Interferon / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015854:Up-Regulation; D000096743:Interferon gamma Receptor; D000098815:T-bet Transcription Factor
chemical_list: D018106:CD28 Antigens; D053804:Granzymes; D006657:Histones; D007371:Interferon-gamma; D053645:Interleukin-2 Receptor alpha Subunit; D008024:Ligands; D016328:NF-kappa B; D052899:Pore Forming Cytotoxic Proteins; D017471:Receptors, Interferon; D053707:Receptors, Interleukin-12; D020825:T-Box Domain Proteins; D051195:Toll-Like Receptor 2; D000096743:Interferon gamma Receptor; D000098815:T-bet Transcription Factor; C508018:Il2ra protein, mouse; C493486:Tlr2 protein, mouse; C483886:perforin, mouse; C509214:Gzmb protein, mouse