Role of TNFRp55 and IL-12p40 in Yersinia enterocolitica O:3 induced arthritis: triggering bacterial antigens and articular immune response.

ELIÇABE J. R.; LACOSTE M.G; GUTIÉRREZ J.V,; DI GENARO M. S.

Rio de Janeiro, Brasil

Congreso; INMUNORIO2007 13th International Congress of Immunology; 2007

International Union of Immunological Societies (IUIS), ALAI, SBI

The pathogenesis of reactive arthritis (ReA), an aseptic synovitis that follows an extra-articular infection, is incompletely known. We studied the impact of TNFRp55 or IL-12p40 deficiency on ReA progression after oral Yersinia enterocolitica O:3 infection, analyzed relevant Yersinia antigens, and intra-articular immune response. Wild-type, TNFRp55-/- and IL-12p40-/- C57BL/6 mice were orogastrically infected with Y. enterocolitica O:3, and monitored for survival and arthritis development. The bacterial load was determined in mesenteric lymph nodes (MLN), the spleen and joints. Articular TNF-a mRNA expression by RT-PCR, and TNF-a protein by ELISA were analysed. Articular Yersinia-specific antibodies were studied by ELISA and dot-blot, and  nitric oxide (NO) by Griess reaction. The survival rate was 75 % in IL-12p40-/-, and 60% in TNFRp55-/- mice. On day 3, both immunodeficient mice showed impaired bacterial clearance in MLN and the spleen (p<0.0006 to p<0.04). Late after infection (day 21 or 52), the bacteria were mostly clarified from MLN, the spleen and joints of all mice. IL-12p40-/- mice developed arthritis on day 21. TNFRp55-/- mice exhibited severe and progressive arthritis from day 21 to 56. Histopathological changes were observed. Increased articular outer membrane protein (OMP)-specific antibodies were detected (p<0.0007 and p<0.04). TNF-a mRNA and protein were increased in joints from TNFRp55-/- (p<0.05) and IL-12p40-/- (p<0.003) mice, but NO levels were impaired in TNFRp55-/- mice  (p<0.02). We concluded that TNFRp55- and IL-12p40-mediated immune mechanisms prevent Y enterocolitica O:3-induced ReA. Yersinia OMP are the relevant antigens. NO induction through TNFRp55 could have a local antibacterial function to prevent ReA.