Activation of iNKT cells prevents Salmonella-enterocolitis and Salmonella-induced reactive artrhitis by down regulating IL-17-producing γδT cells.

NOTO LLANA M; KRUMMEL L; MORALES A; SARNACKI S,; GIACOMODONATO M; BLANCO G; CERQUETTI M

Congreso; Reunión Conjunta de Sociedades de Biociencias. LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica SAIC 2017; 2017

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 103colony 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-galactosyl ceramide (a- GalCer) and γδT activity was blocked with anti-γδT monoclonal antibodies. 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-17produced mainly by γδTcells.