CATHEPSIN L3 PROMOTES IFN-γ RESPONSE BY CD8 T CELLS DURING FASCIOLA HEPATICA INFECTION

CELIAS, D; SILVANE, LEONARDO; CORVO, ILEANA; TORT, JOSE; MOTRAN, CLAUDIA C; CERVI, LAP

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

SAIC-SAI

During its migration through host tissue, the helminth parasiteF. hepatica, secretes a number of distinct cathepsin L cysteinepeptidases. Among them, cathepsin L3 (CL3) is highly expressedin the juvenile larvae, which has the ability to degrade collagen.However, the effect of CL3 on the modulation of immune responseis still unknown. The aim of this work was to study the ability ofCL3 to induce an immune response during F. hepatica infectionin mice. A role of dendritic cells (DC) in this modulation was alsoinvestigated. C57BL/6 mice (B6) were orally infected with 12 F.hepatica metacercariae per animal. After 4 and 17 days postinfection peritoneal cells (PECs) and splenocytes were removed,respectively. These cells were cultured in presence or absence ofCL3 or total parasite lysates (TE) for 48h. Cytokines productionwas detected by ELISA or FACS analysis. Moreover, DC weredifferentiated from B6 bone marrow with GM-CSF and culturedfor 18 h with CL3 (produced in Hansenula polymorpha) or LPS,and injected in B6. After 7 days lymph nodes were obtained andstimulated with CL3. Both PECs and splenocytes from infectedanimals restimulated with CL3, secrete significantly higher levels ofIFN-γ and IL-17 than those observed in uninfected mice (p<0,05).We found that IFN-γ-producing cells in spleen were mostly CD8T cells, and in a lesser extent CD4 T cells, while IL-17-producingcells were not CD4 T cells. Being DC potent antigen presentingcells, we stimulate these cells with CL3, injected them in mice and7 days later we evaluated the response of lymph node cells (LNC )to CL3. CL3-treated DC were able to induce a specific IFN-γ CD8T cells response by LNC from injected animals after CL3 stimulation.Our data show that during F. hepatica infection, CL3 wasable to trigger a specific IFN-γ response by CD8 T cells, beingDC probably involved in this effect. Accordingly, CL3 appears asan interesting target for vaccines development against F. hepatica.