HLA-B27 MODULATES THE SURVIVAL OF SALMONELLA-ENTERITIDIS IN TRANSFECTED L-CELLS, POSSIBLY BY IMPAIRED NITRIC-OXIDE PRODUCTION

Reactive arthritis is triggered by certain microbes that cause primary infections mainly on the gastrointestinal or urogenital mucosa, The d isease is strongly associated with HLA-B27, Long persistence of causat ive microbes or their structures in the body has been thought to have an important role in the pathogenesis of reactive arthritis, This sugg ests that the elimination of the microbes causing reactive arthritis i s ineffective or disturbed in HLA-BZ7-positive individuals developing this complication, We examined the role of the HLA-B27 antigen in micr obe-host interaction in vitro by monitoring the invasion and intracell ular survival of Salmonella enteritidis in mouse fibroblasts transfect ed with HLA-B27, HLA-B7, or beta(2)-microglobulin only, S, enteritidis invaded into all the three transfectants with the same efficiency, Ho wever, at 6 and 10 days after incubation, there were more living intra cellular Salmonella organisms in HLA-B27 transfectants than in the oth er transfected cell lines (P < 0.05), suggesting that the bactericidal effect is impaired in these cells, impaired NO production in HLA-B27- transfected cells was indicated as a possible mechanism, since the amo unt of nitrite in the supernatants of the Salmonella-infected HLA-B27- transfected cells was smaller than that in the supernatants of the Sal monella-infected HLA-B7- or beta(2)-microglobulin-transfected cells (P < 0.001), The inhibition of NO synthesis by N-monomethyl-L-arginine r esulted in impaired elimination of Salmonella also in MLA-B7- and beta (2)-microglobulin-transfected cells. The inverse correlation between i ntracellular survival of Salmonella and the amount of nitrite detected in culture supernatants supports the hypothesis that the L-arginine-d ependent NO pathway plays an important role in the murine fibroblast r esponse against Salmonella. We suggest that a major histocompatibility complex class I antigen, HLA-B27, may contribute to the intracellular persistence of Salmonella by a mechanism which involves the NO pathwa y.