Immune-modulatory effects of the serine protease inhibitor-1 of Toxoplasma gondii on innate immune response

VANESA SÁNCHEZ, MATÍAS PERRONE SIBILIAC, MARIANO PICCHIO, NADIA ARCON, ARIADNA SOTTO, MARÍA DE LOS ANGELES ALDIRICO, IGNACIO FENOY, ALEJANDRA GOLDMAN, VALENTINA MARTIN

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Toxoplasma gondii infects approximatelyone-third of the world population, making it one of the most successfulparasitic organisms. T.gondii serine protease inhibitor-1 (TgPI-1) is a potent inhibitorof neutrophil elastase, trypsin and chymotrypsin but its role during natural infectionis not already known. It has been reported that other serine proteaseinhibitors are able to modulate the immune system. Previously we showed that TgPI-1was able to down-modulate both a Th2 and Th1 type immune responses alreadyestablished. Those results led us to explore the ability of TgPI-1 to modulatethe innate immune response. In this work we used the J774-A1 murine macrophagecell line to study this possible modulatory role. Cells were stimulated withlipopolysaccharide (LPS) or exposed to residual oil fly ash (ROFA), in the presenceof a recombinant form of TgPI-1 (rTgPI-1). We observed that rTgPI-1 was able todecrease nitric oxide production induced by LPS stimulation when compared toLPS alone (p<0.05). No variation was detected in cell viability as measuredby MTT assay or in production of pro-inflammatory cytokines like TNF-α and IL-6. On the other hand, exposure of cells to ROFA showed detrimental effectson cell viability compared to unexposed control cells (p<0.05). Surprisingly,the presence of rTgPI-1 during ROFA treatment restored cell viability to untreatedcell levels, resulting in a significant increment of TNF-α and IL6 secretion compared to ROFA stimulated cells (p<0.05 and p<0.005respectively). The exposure of cells to rTgPI-1 alone showed similar responses tonon-stimulated cells. These results showed the ability of TgPI-1 to modulatethe first steps of the development of immune responses. Our results led uspostulate a possible role of TgPI-1 during T.gondii infection, either diminishing the activation of innate cells thatattack the parasite itself or avoiding cell death during infection, contributingto the establishment of chronic toxoplasmosis