Role of Th17 and Treg cells in septic arthritis and the impact of the Th17/Treg -derived cytokines in the pathogenesis of S. aureus induced septic arthritis in mice. (December 2017)

• Record Type: Journal Article
• Authors: Dey, Ipsita; Bishayi, Biswadev
• Is Part Of: Microbial pathogenesis. Volume 113(2017)
• Page Start: 248
• Page End: 264
• Publication Date: 2017-12
• Subjects: IL-17A -- IL-23 -- Joint inflammation -- Lymphocytes -- Septic arthritis -- Th17/Treg ratio; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2017.10.033
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Intravenous inoculation of Swiss mice with S. aureus leads to severe synovial joint tissue swelling along with prominent T lymphocyte infiltrate with associated inflammation in synovial tissue. Cytokines released from macrophages such as TNF-α, IL-1β and IL-6 the main players that precede cartilage and bone destruction during septic arthritis (SA) followed by osteoclast differentiation and bone resorption. CD4 + naïve T cells upon cytokine driven activation, differentiate into lineages of helper (Th) and regulatory T cells (Treg) including inflammatory Th17 cell lineage. Acting as counterbalance, Tregs protect the host by releasing anti-inflammatory IL-10. A disturbed balance between Th17 and Treg cell development skews the pathways towards Th17 lineage, but how it actually induces SA is still unexplored. Therefore, this study has been attempted to demonstrate the Th17/Treg ratio in synovial tissue, spleen and peripheral blood by FACS and their derived cytokines from serum of arthritic mice. Here, we reported that the ratios of Th17/Treg as well as their related cytokine levels were increased at 3 days post-infection which was decreased during 9 DPI but heightened again at 15DPI resulting in persistence of the disease, though decreased again at 30 DPI even in animals with increased dose of infection. Bacterial colonies were present in synovial joints at 15 DPI in animals with increased infection but found to be absent at 30 DPI. Maintaining Th17/Treg balance by neutralizing functionally active Th17 and their related cytokines or adoptive transfer of fully active Tregs and/or their related cytokines may lead to a novel therapeutic strategy for combating Staphylococcal arthritis. Highlights: Intravenous infection of S.aureus results in disturbance in Th17/ Treg ratio. Th17/Treg ratio by FACS and their derived cytokinesin arthritic mice was studied. Th17 levels were higher at 3DPI and 15DPI. Treg population was higher at 9DPI. The increased Th17/Treg ratio is important in induction of staphylococcal arthritis. Neutralizing Th17 or adoptive transfer of Treg may be a potent therapeutic approach.