Major Histocompatibility Complex Class II Region Confers Susceptibility to Staphylococcus aureus Arthritis

Abstract

The importance of the MHC class II region for the development of septic arthritis was studied in a murine model of haematogenously induced Staphylococcus aureus arthritis. In the first experiment MHC class II deficient mice (Ab ¹=¹ ) and their heterozygous (Ab þ=¹ ) littermates were intravenously inoculated with a single dose of toxic shock syndrome toxin-1 producing S. aureus LS-1 strain. The results demonstrate that the expression of class II MHC molecules increases the prevalence and severity of arthritis. To analyse the impact of MHC class II haplotypes on the disease onset and progression the authors used congenic C3H.NB, C3H.Q and C3H/HeJ mice in the second set of experiments. The results show that C3H/HeJ mice developed the highest frequency and the most severe course of arthritis compared with C3H.NB and C3H.Q animals. Immunohistochemical analysis of arthritic joints revealed equal number of macrophages, CD4 þ and CD8 þ lymphocytes in the inflamed synovia in all the congenic mice. In contrast, the number of MHC class II expressing cells was higher in the arthritic joints of C3H/HeJ mice compared with the congenic strains (P < 0.001). Furthermore, serum levels of proarthrtitogenic cytokines, such as tumour necrosis factor and interleukin-6 were higher in C3H/HeJ group. This study indicates that MHC class II expression is necessary for the development of S. aureus arthritis in mice and that different MHC class II haplotypes confer varying susceptibility for development of joint inflammation induced by staphylococci. A. Tarkowski,

Current status of pathogenetic mechanisms in staphylococcal arthritis

“…We have assessed whether mice that were isogeneic for the major histocompatibility complex (MHC) displayed different outcomes for staphylococcal arthritis. Our results indicated that this was indeed the case, since mice that expressed certain MHC haplotypes were better protected against the infection[28]. Such an outcome may be due to differential expansion capacity of certain T cell receptor families in response to staphylococcal superantigens depending on host MHC background[29].…”

Joint infection

“…Animal models indicate that these bacteria are especially arthritogenic (Bremell and Tarkowski 1995). Using a similar model, MHC class 11 molecular expression were shown to increase the prevalence and severity of arthritis (Abdelnour et al 1997). N itric oxide is an important mechanism used by the macrophage for killing ingested bacteria.…”

Current status of pathogenetic mechanisms in staphylococcal arthritis

“…We have assessed whether mice that were isogeneic for the major histocompatibility complex (MHC) displayed di¡erent outcomes for staphylococcal arthritis. Our results indicated that this was indeed the case, since mice that expressed certain MHC haplotypes were better protected against the infection [28]. Such an outcome may be due to di¡erential expansion capacity of certain T cell receptor families in response to staphylococcal superantigens depending on host MHC background [29].…”