Immune-modulatory properties of the Toxoplasma gondii serine protease inhibitor-1 (TgPI-1)

VANESA R. SÁNCHEZ, IGNACIO M. FENOY, MARIANO S. PICCHIO, ARIADNA SOTO, VALENTINA MARTÍN, ALEJANDRA GOLDMAN.

Los Cocos, Córdoba

Congreso; Reunión Anual Sociedad Argentina de Inmunología; 2013

SAI

Toxoplasma gondii serine protease inhibitor 1 (TgPI-1) is a potent inhibitor of neutrophil elastase, trypsin and chymotrypsin in vitro. It has been shown that other serine protease inhibitors are able to modulate the immune system. In this work we studied the in vitro effects of rTgPI-1 on T helper modulation during an adaptive immune response with Th1 or Th2 profiles and on naïve cells. To assess the modulation of a Th2 response, we used a mouse model of allergy with OVA antigen as allergen. BALB/c mice were sensitized by 2 ip OVA/Al(OH)3 and then aerosol challenged with OVA 3%. Splenocytes from allergic mice were in vitro treated with OVA or OVA+rTgPI-1. The results showed that rTgPI-1 (PI) induced a significant decrease in IL-5 (OVA: 307±46; OVA+PI: 191±30; pg/ml±SEM, p<0,05) and IL-10 (OVA:40±1; OVA+PI:28±7; pg/ml±SEM, p<0,05) levels  in culture supernatants. No variations were detected in IFN- γ secretion.To assess the modulation of a Th1 response, splenocytes from T. gondii chronically infected mice were stimulated in vitro with T. gondii total lysate antigens (TLA). rTgPI-1 induced a significant reduction of IFN-γ and IL-10 production (IFN-γ: TLA: 596±48; TLA+PI; 442±69; pg/ml±SEM, p<0,05; IL-10: TLA: 413±72; TLA+PI; 198±54; pg/ml±SEM, p<0,05). No variations were detected in IL-5 secretion. In contrast, in splenocytes from naÏve mice stimulated with ConA, rTgPI-1 increased the production of Th1 (IFN-γ) and Th2-type (IL-5) cytokines (IFN-γ: ConA: 393±55; ConA+PI: 607,8±81; pg/ml±SEM, p<0,05; IL-5: ConA: 340±72; ConA+PI: 527±71; pg/ml±SEM, p<0,05). These results suggest that rTgPI-1 would be able to down-modulate both a Th2 as well as a Th1--type immune response already established without inducing a change in the polarization. Furthermore, these results show that rTgPI-1 could affect the development of the immune response against antigens during the induction of an adaptive immune response in naive mice.