Co-administration of Toxoplasma gondii serine-protease inhibitor-1 with allergen induces regulatory cells in asthmatic mice

A SOTO, I FENOY, V SÁNCHEZ, MA ALDIRÍCO, M PERRONE SIBILIA, M PICCHIO, N ARCÓN, V MARTIN, A GOLDMAN

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Byusing a therapeutic experimental asthma model we previously showed thattreatment with T. gondii serineprotease inhibitor-1 (TgPI-1) significantly reduced airway hyper-responsivenessand inflammation. Moreover, co-administration of TgPI-1 with the allergenshowed an enhanced improvement compared with the administration of TgPI-1alone. Besides, we observed that allergen-specific Th1 and Th2 responses werediminished. Based on these results, in the present study we sought to explore whetherregulatory cells may account for the effect of TgPI-1. For this purpose we firstevaluated if TgPI-1 treatment modulates allergen-specific T cell proliferation.BALB/c mice ip. sensitized with ovalbumin (OVA)/Alum and aerosol challenged,were intranasally treated with TgPI-1 (PI) or TgPI-1+OVA (OPI). Controlsincluded non-sensitized mice (N), and asthmatic mice treated with PBS (O) or withovalbumin (OO). One week after the treatment, mice were re-challenged. Only micetreated with OPI showed a significant reduction in thoracic lymph node cells OVA-specificproliferation (OPI vs OO; p<0.001). This treatment also induced asignificant increase in CD4+Foxp3+ Treg cells compared tonaïve mice (p<0.05). These resultswere not accompanied by an increase in TGF-β or IL-10 production. A significantexpansion of Tregs (p<0.05) and a diminished allergen specific proliferation(p<0.01) in OPI vs OO groups was also detected at systemic level. Similar tolymph nodes, PI treatment didn´t result in a higher frequency of CD4+Foxp3+cells nor a reduced OVA-specific splenocyte proliferation. These results mightexplain the better outcome of co-administration of TgPI-1 with allergen and suggestthat CD4+Foxp3+ Treg cells might be involved. Functionalstudies will be undertaken to confirm this hypothesis. Overall, TgPI-1 emerges as a promisingtolerogenic adjuvant to be included in therapeutic vaccine formulations