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.

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.

• Authors: Ipsita Dey, Biswadev Bishayi
• Journal: Microbial pathogenesis (Microb Pathog) Vol. 113 Pg. 248-264 (Dec 2017) ISSN: 1096-1208 [Electronic] England
• PMID: 29074430 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Cytokines
• Interleukin-17
• Interleukin-23
• Tumor Necrosis Factor-alpha
• Interleukin-10

Topics

• Animals
• Arthritis, Infectious (blood, immunology, microbiology, physiopathology)
• Bone Resorption
• CD4-Positive T-Lymphocytes
• Cell Differentiation
• Colony Count, Microbial
• Cytokines (metabolism)
• Disease Models, Animal
• Inflammation
• Interleukin-10 (metabolism)
• Interleukin-17 (metabolism)
• Interleukin-23 (metabolism)
• Lymphocytes
• Macrophages (immunology, microbiology)
• Male
• Mice
• Osteoclasts
• Spleen (microbiology)
• Staphylococcal Infections (immunology, microbiology)
• Staphylococcus aureus (pathogenicity)
• Synovial Membrane (microbiology)
• T-Lymphocytes, Regulatory (physiology)
• Th17 Cells (physiology)
• Tumor Necrosis Factor-alpha (metabolism)