Animal model for studying the early stages of reactive arthritis after Salmonella enteritis

NOTO LLANA M; SARNACKI SH; GIACOMODONATO MN; CACCURI RL; BLANCO G; CERQUETTI MC

carlos paz

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008

ReA is a sterile arthritis triggered by a distal mucosal infection.  Studies on ReA pathogenesis are difficult because of the limited tests that can be performed in humans. We describe here a model useful for the study of the early stages of Salmonella ReA.  BALB/c mice were orally infected with 103 CFU of a virulent strain of S. Enteritidis.  After 21 days mice showed gut inflammation and synovitis in the knee joints.  Bacteria was not recovered from joint or draining lymph node cultures at any time point tested, ruling out a septic arthritis.  Specific antibodies against Salmonella were neither detected in plasma nor in joints.  Flow cytometry revealed a significant increase of CD4+ lymphocytes in the popliteal lymph nodes of mice receiving a single oral dose of S. Enteritidis infection.  We investigated the local response to a second exposure to the antigen challenging infected mice in the footpad with heat-killed Salmonella.  Results showed a higher percent of CD4+ lymphocytes in the popliteal lymph nodes, compatible with a secondary response to Salmonella.  Using a invG mutant we found that the proinflammatory signalling mediated by Salmonella type 3 secretion system-1 (TTSS-1) in the gut is required for the induction of joint sequelae. This highly reproducible and easy to perform model provides great potential for investigating both host and bacterial contributions to ReA.