Death of adrenocortical cells during murine acute T. cruzi infection is not associated with TNFR1 signaling but mostly with the type II pathway of Fas‐mediated apoptosis

ANA ROSA PÉREZ ; FLAVIA LAMBERTUCCI; FLORENCIA B. GONZÁLEZ; EDUARDO ROGGERO; OSCAR BOTTASSO; JULIANA DE MEIS; MARIA T. RONCO; SILVINA R VILLAR

BRAIN BEHAVIOR AND IMMUNITY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2017

0889-1591

Earlier studies from our laboratory demonstrated that acuteexperimental Trypanosoma cruzi infectionpromotes an intense inflammation along with a sepsis-like dysregulated adrenal response characterized by normallevels of ACTH with raised glucocorticoid secretion. Inflammation was also known to result inadrenal cell apoptosis, which in turn may influence HPA axis uncoupling. Toexplore factors and pathways which may be involved in the apoptosis of adrenalcells, together with its impact on the functionality of the gland, we carriedout a series of studies in micelacking death receptors, such as TNF-R1 (C57BL/6-Tnfrsf1atm1Imx orTNF-R1-/-) or Fas ligand (C57BL/6 Fas-deficient lpr mice), undergoing acute T.cruzi infection. Here wedemonstrate that the late hypercorticosterolism seen in C57BL/6 mice duringacute T. cruzi infection coexistswith and hyperplasia and hypertrophy of zonafasciculata, paralleled by increased number of apoptotic cells. Apoptosisseems to be mediated mainly by the type II pathway of Fas-mediatedapoptosis, which engages the mitochondrial pathway of apoptosis triggering the cytochromec release to increase caspase-3 activation. Fas-induced apoptosis ofadrenocortical cells is also related with an exacerbated production ofintra-adrenal cytokines that probably maintainthe late supply of adrenal hormones during host response. Present results shedlight on the molecular mechanisms dealing with these phenomena which arecrucial not only for the development of interventions attempting to avoid adrenal dysfunction, but also for its wideoccurrence in other infectious-based critical illnesses.