APOPTOSIS SIGNALING PATHWAYS IN ADRENAL GLANDS DURING EXPERIMENTAL TRYPANOSOMA CRUZI INFECTION

VILLAR S; MARTINELLI R; GONZÁLEZ FB; ROGGERO E; PÉREZ AR; RONCO MT; BOTTASSO OA

Mar del Plata

Congreso; LIX Reunión Científica Anual de la Sociedad Argentina de Inmunología (SAI).; 2014

Sociedad Argentina de Inmunología

TNFR1 andFas share an intracellular domain crucialto induce apoptosis by triggering the initiator caspase-8and subsequently the effector caspase 3; or could induce pathways that are involved in the inflammatoryresponse including NF-κB and MAPK pathways. At adrenal level bothpathways might influence glucocorticoid (GC) synthesis during an inflammatoryprocess. We previously showed that during T.cruzi (Tc) infection MAPKand NF-κB pathways regulate the expression of enzymes involved in GC synthesis. Now we aimed to evaluate whether TNFα and FasL participatethrough their respective death receptors on adrenal cell apoptosis. We studied this issue infected withTc C57BL/6 mice (B6) and mice deficient in TNFR1 (R1) and Fas (lpr mice). Controls were inoculated with saline solution (Co). Data was obtained at day 17post-infection and expressed as mean ± SEM (n=5/group).  Histological evaluations showed increased values ofadrenal apoptotic index (AI) in all infected groups, despite Tc-lpr displayed a minor AI compared withTc-B6 and Tc-R1 (AI%; number ofapoptotic bodies/total cell number x 100); Tc-B6: 5.0±0.4*; Tc-R1: 5.0±0.5*; Tc-lpr: 1.2±0.2*#&. Caspase 8 activity was enhanced inTc-B6 group compared to Tc-R1 and Tc-lprmice (Relative activity; Tc-B6/Co-B6: 0.85±0.07, Tc-R1/Co-R1:0.60±0.08#,Tc-lpr/Co-lpr: 0.68±0.07#). Caspase 3 activity was augmented inall infected groups compared to their respective Co group (p<0.05), but without differences between infectedones. Adrenal lipoperoxidation (LP) were also evaluated as a signal of oxidative stress-induced apoptosis by HPLC. LP was only observed in the Tc-R1 group. In addition, Bax expression wasdiminished in Tc-lpr compared to therest of infected mice (p<0,05). *p<0.05 vs uninfected counterparts, #p<0.05 vs Tc-WT, &p<0.05vs R1. Our results showed that adrenal apoptosis are mainly triggered by Faspathway. In R1 mice the results suggest that mechanisms inducing LP triggeredapoptosis during infection.