ROLE OF MYELOID-DERIVED SUPPRESSOR CELLS DURING Trypanosoma cruzi INFECTION OF TSf-ISPA IMMUNIZED MICE

GAMBA JC,; ROLDÁN C, ; PROCHETTO E, ; BONTEMPI I, ; LUPI G; GONZÁLEZ F; PACINI F,; PONCINI C; VERMEULEN M; PÉREZ AR; MARCIPAR I; CABRERA G

Tucumán

Congreso; LXVII Reunión científica anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

Introduction: Previously, we reported that vaccination with a trans-sialidase-based antigen (TSf) formulated with a cage-like particle adjuvant (ISPA) confers protection against Trypanosoma cruzi (T.cruzi). TSf-ISPA-immunization increases mice survival, reduces parasitemia and decreases the number of spleen myeloid-derived suppressor cells (MDSCs, CD11b+GR1+) in vaccinated and infected animals at day 21 postinfection.Aim: Study the influence of MDSCs on the effector response in TSf-ISPA-immunized and T.cruzi-infected mice.Methods: Tree doses of TSf-ISPA were given to BALB/c mice before infection with 1000 Tulahuen trypomastigotes. 5-fluorouracil (5FU) (50mg/kg) was given at day 15 postinfection to deplete MDSCs. At 21-day postinfection flow cytometry was used to measure iNOS, CD11b, Gr1, Ly6G, Ly6C, CD8a, CD107, CD44, CD4, Ki-67, CD11c and CD80 in splenocytes. ELISA was used to measure plasma levels of IFN-ɣ.Results: Survival after infection: TSf-ISPA-immunized mice: 100%; TSf-ISPA and 5FU-treated mice: 60-100%; PBS-treated mice: 60-80% PBS and 5FU-treated mice: 0%. 5FU treatment strongly decreased the number of MDSC iNOS+ splenocytes in TSf-ISPA-immunized and infected mice (TSf-ISPA-Tc+ 5FU), compared to PBS-treated or TSf-ISPA-immunized mice, (both infected, non-treated with 5FU) (p