Role of TNFRp55 in Yersinia enterocolitica O:3-induced arthritis: triggering bacterial antigens and articular immune response.
OBJECTIVE
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.
Di Genaro
M S
MS
Laboratory of Microbiology and Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, 5700, San Luis, Argentina. sdigena@unsl.edu.ar
Cargnelutti
D E
DE
Eliçabe
J R
JR
Lacoste
M G
MG
Valdez
S
S
Gómez
N
N
de Guzmán
A M S
AM
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016918:Arthritis, Reactive / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004198:Disease Susceptibility; D007596:Joints / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015009:Yersinia Infections / Q000276:immunology* / Q000473:pathology; D015008:Yersinia enterocolitica / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide