title: Toll-like receptor 2 and 6 interdependency in the erosive stage of Staphylococcus aureus induced septic arthritis mediated by IFN-γ and IL-6--A possible involvement of IL-17 in the progression of the disease.
abstract: Staphylococcus aureus induced septic arthritis has emerged as a potent disabling and life threatening disease; hence combating this malady has become an imperative need of medical science. Role of TLR-2 in innate recognition of S. aureus and activation of inflammatory cascade by the interplay of some proinflammatory cytokines, resulting in joint inflammation has been established. Variation in the reports suggesting both functional dependency and independency of TLR-2 on its heterodimeric partner TLR-6 in response to ligands exists, thus this study was postulated to observe the expression pattern of TLR-6 in synovial tissue and lymphoid organs after inducing septic arthritis by S. aureus in Swiss albino mouse model and the instigated cytokine profile could affirm its plausible role in SA. The functional relation of TLR-2 and 6 was verified by simulating an in vitro study design on synovial mononuclear cells, blocking TLR-2 and 6, and it was found that they are required to co-express for generating cytokine, NO and H2O2 on infection. IFN-γ, IL-6 and IL-17 were identified to play a distinguished role in SA from their secretion pattern in both in vivo and in vitro study. IFN-γ and IL-6 remained high throughout the infection possibly by the shift of response from Th1 to Th2 and Th17 and contribute in various converging pathways of inflammation. IL-17 increased with the onset of the disease but reduced on the late period. Hence IFN-γ, IL-6, IL-17 along with TLR-6 can be a potent target for therapeutic approach because of their significant contribution in SA.
authors.affiliation: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Kolkata 700009, West Bengal, India.
authors.forename: Chandrayee
authors.initials: C
authors.lastname: Ghosh
authors.affiliation: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Kolkata 700009, West Bengal, India. Electronic address: biswadevbishayi4@gmail.com.
authors.forename: Biswadev
authors.initials: B
authors.lastname: Bishayi
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology* / Q000382:microbiology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051216:Toll-Like Receptor 6 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C556062:IL10 protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; C493486:Tlr2 protein, mouse; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; D006861:Hydrogen Peroxide
keywords: Lymphoid organs; Neutralization; Septic arthritis; Swiss albino mouse; Synovial mononuclear cells; Toll-like receptor 6 (TLR-6)