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

PERRONE SIBILIA M; MARTIN V; SOTO ARIADNA; ALDIRICO V; FENOY IGNACIO; FARIAS ANA; BERGUER PAULA; GOLDMAN ALEJANDRA

Mar del Plata

Congreso; Reunión anual SAI; 2019

In view of the increased prevalence of atopic disorders and the side effects of current treatments, new strategies for intervention in allergic diseases are needed. New therapies have focused on the deviation of the response towards a Th1 phenotype and also in restoring regulatory responses. Serine-proteases are important players in the pathogenesis of asthma, promoting inflammation and tissue remodeling. On the other hand, it?s also known that many serine protease inhibitors display immunomodulatory properties. We previously showed that treatment with T. gondii serine protease inhibitor-1 (rTgPI-1) significantly reduced experimental asthma. Co-administration of rTgPI-1 with the allergen showed an improvement compared with the administration of rTgPI-1 alone, suggesting that this inhibitor may function as a tolerogenic adjuvant. To study the mechanism behind rTgPI-1 immunomodulatory activity, we studied its effect on dendritic cells (DCs). Particularly, we aim to study the profile and functionality of the DCs differentiated in presence of rTgPI-1Results show that the addition of rTgPI-1 seems to generate DCs unresponsive to LPS maturation, showed by its decrease in the costimulatory signal and proinflammatory cytokines secretion. Moreover, DCrTgPI-1 co-culture with C57BL/6 in a mix lymphocyte reaction show a lower capacity of these APC to induce both T CD4+ activation and type 2 and type 3 immune responses. Instead an increase in the percentaje of Foxp3+ CD4+ regulatory T cells was observed. Collectively, the addition of TgPI-1 generates tolerogenic DCs, with a seminature phenotype, able to reduce inespecific T cells responses, promoting regulatory responses.