Toxoplasma gondii serine-protease inhibitor-1: a new adjuvant candidate for asthma therapy

SOTO A; FENOY IM; SANCHEZ VR; MARCH F; PERRONE M; ALDIRICO MA; PICCHIO MS; ARCÓN, NADIA; ACOSTA P; POLACK F; MARTIV V; GOLDMAN A

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2017

1932-6203

Serine-proteases are important players inthe pathogenesis of asthma, promoting inflammation and tissue remodeling. It?s alsoknown that many serine protease inhibitors display immunomodulatory properties.TgPI-1 is a Toxoplasma gondii proteinthat exhibits broad spectrum inhibitory activity against serine proteases. Inview of the increased prevalence of atopic disorders and the need to developnew treatment strategies we sought to investigate the potential of TgPI-1 fortreating respiratory allergies. For this purpose, we developed a therapeuticexperimental model. BALB/c mice were rendered allergic by intraperitonealovalbumin-alum sensitization and airway-challenged. Once the asthmaticphenotype was achieved, mice were intranasally treated with rTgPI-1 alone or witha mixture of rTgPI-1 and ovalbumin (OVA). A week later mice were given asecondary aerosol challenge. Treatment with rTgPI-1 alone or co-administeredwith OVA diminished bronchoalveolar eosinophilia, mucus production and peribronchiallung infiltration. This effect was accompanied by a lung resistance reductionof 26.3% and 50.3% respectively. Both treatments resulted in the production of lowerlevels of IL-4, IL-5, IFN-γ and regulatory IL-10 by thoracic lymph nodecells stimulated with OVA. Interestingly, significant decreases in OVA specific IgE and T cellproliferation, and increases in FoxP3+ T cells at local and systemiclevels were only detected when the inhibitor was administered along with OVA. Theseresults show that both rTgPI-1 treatments reduced asthma hallmarks. However,co-administration of the inhibitor with the allergen was more effective. Hence,rTgPI-1 emerges as a noveladjuvantcandidate for asthma treatment