T. gondii serine protease inhibitor-1 (TgPI-1) modulates dendritic cell maturation

A SOTO; P BERGUER; A GOLDMAN; M PERRONE SIBILIA; I FENOY; A FARÍAS; V MARTÍN

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología 2018; 2018

SAI

T. gondii serine protease inhibitor-1 (TgPI-1) modulates dendriticcell maturation We previously showed that treatment with arecombinant T. gondii serine proteaseinhibitor-1 (rTgPI-1) significantly reduced experimental asthma. Co-administrationof rTgPI-1 with the allergen showed an improvement compared with theadministration of rTgPI-1 alone, suggesting that this inhibitor may function asa tolerogenic adjuvant. To further study the mechanism behind TgPI-1 immunomodulatoryactivity, we aimed to study the effect of this protease inhibitor on dendriticcells (DCs). Murine DCs were obtained from BALB/c mice bone-marrow precursors, culturedfor nine days with GM-CSF and then stimulated with LPS. rTgPI-1 (depleted fromendotoxin) was added following three different protocols: rTgPI-1 was added a) duringdifferentiation (day 3-9), b) to immature DCs or c) to DCs matured with LPS. A diminished percentage of CD11+MHCII+ DCs wereobtained when rTgPI-1 was added during differentiation (p<0.001). No differencesin the expression of activation markers, CD80 and CD86, measured by flowcytometry, were detected. While no changes were observed in culture supernatantIL-6 and IL-10 cytokines, a significantly diminished IL-12 production wasdetected (p<0.01). When we analyzed the effect of rTgPI-1 on immature-DCs, surprisingly,we observed a different outcome than the expected. Indeed, rTgPI-1 was able tomature DCs (p<0.01) and promote IL-12 secretion (p<0.01), similar toresponses induced by LPS. Finally, while addition of rTgPI-1 to LPS-activateddendritic cells showed no differences in cell-surface expression of CD80 andCD86 a significantly less secretion of IL-12 (p<0.05) was registered. Furthermoreand interestingly, an increased ratio of IL-10 vs. IL-12 was observed (p<0.01).Altogether these results show that rTgPI-1 couldinterfere with DCs differentiation and, on the other hand, induce different maturationprofiles depending on the cell status. Although further analyses are necessary,data obtained from the effect on matured DCs may account for the in vivo results previously observed.