T cell subpopulations in inflammasome nlrp3-/- mice during the acute infection with Trypanosoma cruzi

PAROLI AUGUSTO; GONZALEZ PATRICIA; GEA SUSANA

Congreso; IV LASID Meeting, LXIII Argentinean Society for Immunology Meeting and II French Society for Immunology Meeting; 2015

Background: NLRP3 inflammasome activation, as well as other innate receptors, plays a crucial role during T. cruzi infection. We have previously demonstrated an increase of IL-1beta-producing F4/80+ intra-hepatic leukocytes (IHL) associated with NLRP3 and TLR9 up-regulation. The aim of this work was to evaluate the involvement of NLRP3 on the expansion of CD4+, CD8+ T lymphocytes and F4/80+ IHL in addition to the production of reactive oxygen species (ROS) and nitric oxide (NO) by macrophages.Methods: Male C57BL/6 WT and nlrp3-/- mice were infected with T. cruzi (1000 i.p. injected-Tulahuen strain). The number of CD4+ and CD8+ T cells, IL1R, IL18R expression and intracellular cytokine production, as well as the detection of ROS and NO in F4/80+ IHL were evaluated at 14 and 21 dpi by flow cytometry.Results: Nlrp3-/- animals showed an increased F4/80+ IHL number (p<0.001) which produced NO, ROS or IL-10 at 14 and 21 dpi. Mutation of nlrp3 increased IL18R though did not alter the IL1R expression on CD4+ cells. Besides, CD4+IL4+ cell number decreased at 14 and 21 dpi (p<0,001) although CD4+IL10+ leukocyte number increased at the end of the infection. On the other hand, CD8+IFNg+ and CD8+IL-10+ cells were augmented in KO animals. Furthermore, CD8+IL1R+ cells decreased at 21 dpi though the expression of IL18R kept heightened along the infection.Conclusion: These results suggest that NLRP3 would regulate IL-18R signaling and favour the induction of CD4+IL4+ cells. This receptor would also control IL10+ T lymphocytes expansion and modulate CD8 T cell populations in the liver of T. cruzi infected mice.