Accelerated onset of arthritis by systemic infection of Mycoplasma fermentans in the knock-in mice gp130F759

Abstract

Abstract Development of autoimmune diseases is influenced by both genetic and environmental factors. The knock-in mouse gp130F759 having a point mutation Y759F in gp130, a signaling receptor subunit for IL-6 family cytokines, spontaneously develops arthritis like rheumatoid arthritis (RA) at 8 months old (M.O.) by aberrant IL-6 signals. Mycoplasma fermentans (Mf) was reported to exist in the synovial fluid of RA, but its pathogenic role has not been clarified. In this study, we examined the effects of systemic infection with Mf on the arthritis of gp130F759, and the cellular changes in the synovium. Gp130F759 at 3 M.O. with no symptoms of arthritis were infected with Mf via vein. The clinical scores based on the restriction of joint flexibility were determined from day 3 to 28 after infection. At 1 month after infection, the group with Mf infection had significantly higher total scores of 4 limbs than the group at the same age without infection. Additionally, the cellular populations and numbers in the synovium were analyzed with flowcytometry. The kinetics study revealed that the numbers of the synovial cells predominated by neutrophils increased at day 10 and 28 after infection. To verify the roles for neutrophils increased, 0.25 mg of anti-Gr-1 antibody was injected intraperitoneally at 9 days after infection. The group of treated mice showed no increases of the clinical scores and the synovial cells at 1 month after infection. These data indicated that systemic infection of Mf induces neutrophil-dependent facilitation of arthritis in gp130F759. We propose that this model is useful to clarify the molecular events caused by microorganisms at the preclinical phase of RA.