DEPLETION OF MYELOID-DERIVED SUPPRESSOR CELLS CAUSES DENDRITIC CELLS INCREASES DURING IMMUNIZATION AGAINST TRYPANOSOMA CRUZI

ESTEFANÍA PROCHETTO; ELIANA BORGNA; JUAN CRUZ GAMBA; FLORENCIA PACINI; CAROLINA PONCINI; MÓNICA VERMEULEN; ANA ROSA PEREZ; IVÁN MARCIPAR; GABRIEL CABRERA

San Luis

Congreso; LXX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) & 3ER CONGRESO FRANCO-ARGENTINO DE INMUNOLOGÍA (FAIC); 2023

Sociedad Argentina de Inmunología

Introduction: Chagas Disease is caused by the protozoan parasite Trypanosomacruzi (T. cruzi). To date, there is no prophylactic or therapeutic vaccine available.We have reported that a vaccine based on a trans-sialidase fragment (TSf)formulated with a cage-like particle adjuvant (ISPA) protects BALB/c mice againstT. cruzi infection. We also described that depletion of CD11b+Gr-1+myeloidderived suppressor cells (MDSCs) with 5-fluorouracil (5FU) during TSf-ISPAimmunization potentiated the protective capacity of the vaccine candidate.Aim: To study whether MDSC depletion influences spleen and lymph nodedendritic cells (DCs) numbers during the immunization phase, and whetherMDSCs from immunized mice are able to suppress maturation of DCs in vitro.Methods: 3 doses of TSf-ISPA were given to BALB/c mice, with a 15-day intervalbetween each dose. 5FU (50mg/Kg) was given one day before and 8 days aftereach TSf-ISPA inoculation. Spleen and lymph node CD11c+ DCs andconventional type I CD11c+CD8α+dendritic cells (cDCI) were measured by flowcytometry in PBS-inoculated and double 5FU-TSf-ISPA vaccinated mice, at day2 and 7 post-immunization (p.imm). In addition, Gr-1+ splenocytes were purifiedby magnetic cell sorting from TSf-ISPA immunized mice (without 5FU) and thecapacity to suppress the expression of MHCII and CD80 was assessed in vitrousing bone-marrow derived dendritic cells (BMDCs).Results: The absolute number of CD11c+ DCs and CD11c+CD8α+cDCIsignificantly increased in TSf-ISPA-immunized mice that were depleted ofMDSCs with 5FU. For instance, at day 7 p.imm. mean number of CD11c+ (DCs)splenocytes x106 ± standard deviation (SD): PBS-treated mice: 3,05±0,4; double5FU-TSf-ISPA mice: 5,1±0,3 (p