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

ARIADNA SOTO, IGNACIO FENOY, VANESA SÁNCHEZ, MARÍA ALDIRICO, MATÍAS PERRONE SIBILIA, MARIANO PICCHIO, NADIA ARCÓN, PATRICIO ACOSTA, VALENTINA MARTÍN, ALEJANDRA GOLDMAN.

Congreso; First LASID-SAI-FAIC Meeting; 2015

Immunotherapy is an alternative for asthma treatment. Using an experimental asthma model, we have shown that treatment with TgPI-1 plus allergen (PI+OVA) reduced lung eosinophilia and mucus production. Herein, we evaluated whether TgPI-1 treatment alone (PI) improve asthma symptoms. BALB/c mice were ip. sensitized with OVA/Alum and aerosol challenged. Later, they were intranasally treated with PI (PI) or PI+OVA (OPI). Controls included non-sensitized mice treated with PI alone (NPI), and sensitized mice treated with PBS (O) or OVA (OO). One week later, mice were re-challenged. PI and OPI groups showed reduced airway hyperresponsiveness (NPI:2,7±0,2; Ob:3,7±0,5; OOc:5,3±0,5; PId:2,8±0,2; OPIe:2,3±0,2; cmH2O.s/mL±ES,*, p<0,001 c vs e). Lung histopathology exhibited decreased mucus production (NPI:0,5±0,1; Ob:2,4±0,1; OOc:2,2±0,1; PId:1,7±0,3; OPIe:1,6±0,1; índice±ES, #, p<0,1 b vs d) and peribronchial and perivascular lung infiltrates (NPI:2±0,1; Ob:8,8±0,3; OOc:8,3±0,4; PId:7,3±0,55; OPIe:6,7±0,37; índice±ES, #). IL-4, IL-5, IFN-γ and IL-10 production was reduced in thoracic lymph node cells from PI treated mice (IL-4: NPI:0±0; Ob:970,4±98,1; OOc:885,1±79,2; PId:392,6±126; OPIe:523,8±67,3 pg/ml±ES*#, IL-5: NPI:0±0; Ob:1900±165,2 OOc:1588±180,9; PId:1031±201,5; OPIe:875,6±167,3 pg/ml±ES*#; IFN-γ: NPI:0,0±0,0; Ob:60,93±8,3; OOc:39±7,9; PId:20,95±10,5; OPIe:13,5±4,6 pg/ml±ES,*#; IL-10: NPI:25,6±225,6; Ob:2092±571; OOc:2275±600,7; PId:336,8±143,4; OPIe:933,1±355,6 pg/ml±ES, *;p<0,1 c vs e). A trend to increased TGF-β (NPI:730,3±99,53; Ob:155,2±53,15; OOc:574,0±315,5; PId:470,0±167,5; OPIe1274±492,2 pg/ml±ES) was detected in OPI group. *p<0,05 b vs d, #p<0,05 c vs e. Both PI treatments reduced asthma halmarks, however OVA+PI was more effective. This difference could be due to increases in TGF-β, but the immunological mechanisms should be further studied. This results show that TgPI-1 has a better potential as an adjuvant therapy.