The B lymphocyte in Staphylococcus aureus arthritis

Abstract

Joint infection caused by Staphylococcus aureus leads to heavy synovitis and rapid destruction of bone and cartilage. Permanent loss of joint function is seen in 20-50% of the patients, despite early eradication of the bacteria with antibiotics. The morality rate, 5- 25%, is due to an exaggerated immunological reaction by the host in response to the bacteria. The mechanisms behind this phenomenon are not fully understood. The murine model of hematogenously induced S. aureus sepsis and septic arthritis provides unique possibilities tostudy the host-bacterium relationship. Using this model we have analysed the role of B lymphocytes and their products for the development and progression of S. aureus induced arthritis and sepsis. We have found that mice completely devoided of mature B cells and immunoglobulins (µ-MT-mice) and CD22-deficient mice (having a 75% reduction of marginal zone B cells) do not differ in the outcome of S. aureus induced arthritis and sepsis as compared to intactcontrol mice. Neither did mice deficient for the activational IgG receptors, FcgRI and FcgRIII, differ in rate and severity of arthritis or mortality numbers, as compared to control mice. Incontrast, presence of FcgRIIb led to increased mortality rate as compared to FcgRIIb knockout mice, probably due to decreased phagoyctosis and impaired bacterial clearance. In addition, FcgRIIb-deficient animals displayed elevated levels of protecting Clumping factor A antibodies and IL-10 as compared to controls, both contributing to host protection. Further, we have shown that mice deficient for IL-10 exhibited aggravated arthritis and an increasedbacterial load. Exploring the intracellular cytokine content in B cells, we found that stimulation in particular with TSST-1 led to a substantial production of IFN-g early during the infection. The number of B cells expressing IL-10 or IL-4 increased during the first week of infection contributing to a diminished number of IFN-g positive cells. Thus, mature B cells and their products do not contribute to host protection or pathogenicity of S. aureus induced arthritis and sepsis. Absence of FcgRIIb decreases the mortality probably due to increased bacterial clearance and elevated IL-10 levels in additionto production of protective Clumping factor A antibodies. The presence of IL-10 per se contributes to increased bacterial clearance and amelioration of the arthritis.