INVESTIGADORES
FENOY Ignacio Martin
congresos y reuniones científicas
Título:
Dendritic cell functionality is modulated by Toxoplasma gondii serine protease inhibitor-1 (TgPI-1)
Autor/es:
ARIADNA SOTO; A FARIAS; M PERRONE SIBILIA; ALDIRICO MA; V MARTÍN; PAULA BERGUER; FENOY, I; GOLDMAN ALEJANDRA
Reunión:
Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019
Resumen:
Background: We have previously showed that TgPI-1 may function as a tolerogenic adyuvant in an asthma model. To study the mechanism behind TgPI-1 immunomodulatory activity, we studied its effect on dendritic cells (DCs). To that end this inhibitor was added during BMDC differentiation (DCTgPI-1). Significantly diminished IL-12 production and CD80 and CD86 expression was detected upon dendritic cell stimulation. Aim: Herein we further study the DCTgPI-1 profile and functionality.Methods: Murine DCs were obtained from BALB/c mice bone-marrow precursors, cultured for nine days with GM-CSF in the presence or absence of rTgPI-1 (depleted from endotoxin) and then stimulated with LPS. Subsequently, to analyze BMDC function a mix lymphocyte reaction (MLR) was done co-culturing these cells with naïve C57BL/6 mice splenocytes. Results: Besides expressing lesser levels of CD80 and CD86, DCTgPI-1 showed significantly less expression of CD40. In addition, IL-12 and IL-6 secretion was diminished while no changes were observed in IL-10 production. As a consequence, IL-10/IL-12 ratio increased in DCTgPI-1. Co-culture of mature DCTgPI-1 with C57BL/6 splenocytes showed decreased T cell activation, measured by CD69+ expression either on CD4+ or CD8+ population. Accordingly, T cell proliferation was also diminished. MLR supernatants, showed significantly less IL-6. No differences in IL-10 and IFN-γ levels were detected. Furthermore, we observed a significantly higher percentage of CD4+FoxP3+ cells. Similar results were obtained when all the experiments were carried out with BMDC-purified CD11c+ cells. Conclusions: These results show that rTgPI-1 could interfere with BMDCs differentiation rendering these cells immature and able to prime regulatory responses.