ACTIVATION OF iNKT CELLS PREVENTS Salmonella-ENTEROCOLITIS AND Salmonella-INDUCED REACTIVE ARTRHITIS BY DOWNREGULATING IL-17-PRODUCING γδT CELLS

KRUMMEL LUCIA; GIACOMODONATO; NOTO LLANA M; SARNACKI SH; CERQUETTI MC; MORALES, ANDREA L.; BLANCO, GUILLERMO

buenos aires

Congreso; Reunión conjunta de sociedades biocientificas; 2017

Reunión conjunta de Sociedades Biocientificas,

Background: Reactive arthritis (ReA) is a sterile joint inflammation as a sequel to Salmonella gut infection. We have previously demonstrated that the severity of joint lesions is directly related with the intestinal levels of IL- 17 generated during S. Enteritidis infection. γδT lymphocytes are a possible source of IL-17. It has been suggested that γδT responses are modulated by iNKT cells, therefore, here we analyze the involvement of γδT and iNKT cells on Salmonella-induced ReA. Methods: Adult female BALB/c mice received 3-4 x 103 colony forming units of S. Enteritidis by the gastrointestinal route. Studies were performed 1 and 5 days after infection. Mesenteric lymph node γδT population was achieved by flow cytometry after enterocolitis onset. iNKT cell activation was studied using alpha-galactosylceramide (a- GalCer) and γδT activity was blocked with anti- γδT monoclonal antibody. Then, histological tissue evaluation and mesenteric IL-17 expression by qPCR were assessed. Results: We found that during S. Enteritidis infection the total number of γδT cells is increased in mesenteric lymph nodes. Infected mice treated with a-GalCer showed diminished intestinal and joint lesions concomitantly with a significant decrease in mesenteric IL-17 expression. Animals suffering from enterocolitis treated with anti- γδT antibody presented the same phenomenon. In addition, mesenteric γδT population was decreased in number in a-GalCer treated animals. Conclusions: Our results indicate that activation of iNKT cells renders protection against Salmonella ReA. This beneficial effect of a-GalCer treatment would be related to the decrease in IL-17 produced mainly by γδT cells.