ASSESSMENT OF BENZNIDAZOLE AND CCR4 ANTAGONIST COMBINATION FOR Trypanosoma cruzi CHRONIC INFECTION TREATMENT

PROCHETTO IVÁN ; CAROLINA ROLDÁN; BONTEMPI IVÁN; VICCO MIGUEL; RODELES LUZ; CABRERA GABRIEL; GIULIANA LUPI; ROLDAN CAROLINA; GONZALEZ LIHUE; PEVERENGO LUZ; MARCIPAR IVÁN

CABA

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Benznidazole (Bz) is the main drug used to treat T. cruzi infection Besides its parasiticide effect it is able to stimulate T cell specific effectorresponses. Taking in mind that this immunological modulationhas shown to be important for parasite eradication, in this work wehypothesized that the efficacy of Bz treatment could be improvedby inhibiting T regulatory cells, using a CCR4 antagonist receptor(CCR4a). BALB/c mice were infected with 106 trypomastigotes ofSylvio T. cruzi strain. Treatment was administered at 120 days postinfection (dpi) and groups were assigned as follow: CCR4a+Bz(treated with subcutaneous CCR4a and oral administration of Bz100 mg/kg); CCR4a alone; Bz alone (100 mg/kg); PBS (untreatedinfected group) and NI (non-infected group). At 188 and 273 dpi,parasitemia was evaluated by qualitative PCR. Also, specific IgG1and IgG2a levels were measured by indirect ELISA. At 273 dpi, electrocardiograms(ECG) were carried out and heart parasite load wasdetermined by PCR real time. In all infected groups, the presence ofthe parasite was found before and after different treatments. Heartparasite load at day 273 was not significantly different in all infectedgroups. Levels of specific antibodies were meaningfully increasedin all groups after treatment (p