Role of TNFRp55 in Yersinia enterocolitica O:3 induced arthritis: triggering bacterial antigens and articular immune response

M. S. DI GENARO; D. E. CARGNELUTTI; J, R. ELIÇABE; M.G. LACOSTE; S. VALDEZ; N. GÓMEZ; A. M. S. DE GUZMÁN

RHEUMATOLOGY (OXFORD, ENGLAND)

Oxford University (British Society of Rheumatology)

Lugar: Oxford, Inglaterra; Año: 2007 vol. 46 p. 590 - 596

1462-0324

OBJECTIVES:The pathogenesis of reactive arthritis (ReA), an aseptic synovitis that follows an extra-articular infection, is incompletely known. We studied the impact of tumour necrosis factor receptor (TNFR) p55 deficiency on the progression to ReA after oral Yersinia enterocolitica O:3 infection, the Yersinia antigens triggering articular inflammation and a possible articular TNFRp55-mediated mechanism that protects against ReA.METHODS:Wild-type C57BL/6 and TNFRp55-/- 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 (MLNs), the spleen and joints. Interferon (IFN)-gamma, TNF-alpha and IL-10 mRNA expression in MLN and joints were analysed by reverse transcription-polymerase chain reaction (RT-PCR). Articular antibodies to Yersinia antigens, TNF-alpha protein and nitric oxide (NO) levels were assessed. Acute arthritis was evaluated after joint injection of Yersinia antigens.RESULTS:The survival rate was 60% in TNFRp55-/- mice. They showed impaired bacterial clearance in MLN, the spleen and joints, and excessive mRNA expression of pro-inflammatory cytokines in MLN. Clinical and histological examinations revealed that TNFRp55-/- mice developed severe arthritis. Moreover, augmented articular outer membrane protein (OMP)-specific antibodies and TNF-alpha but impaired NO levels were detected in TNFRp55-/- mice. Synovial inflammatory response was detected by joint OMP injection.CONCLUSIONS:TNFRp55-mediated immune mechanisms prevent ReA development after oral infection with Y. enterocolitica O:3. Yersinia OMPs are the relevant antigens triggering ReA. NO induction through TNFRp55 signalling could have a local antibacterial function to prevent ReA. This study could contribute to ReA-specific therapeutic studies.