Rheumatology Advance Access originally published online on October 13, 2006
Rheumatology 2007 46(4):590-596; doi:10.1093/rheumatology/kel348
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Role of TNFRp55 in Yersinia enterocolitica O:3-induced arthritis: triggering bacterial antigens and articular immune response
Laboratory of Microbiology and Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, 5700, San Luis and 1LARLAC (CONICET) Faculty of Medicine, National University of Mendoza, 5500, Mendoza, Argentina.
Correspondence to: M. S. Di Genaro, Laboratory of Microbiology and Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, 5700, San Luis, Argentina. E-mail: sdigena{at}unsl.edu.ar
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Abstract |
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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)-
, TNF-
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- 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- 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.
KEY WORDS: Yersinia enterocolitica, Reactive arthritis, TNFRp55, Oral infection, Mice, Bacterial antigens, Nitric oxide
Submitted 2 July 2006;
revised version accepted 8 September 2006.
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