Apoptosis hepatocelular durante la infección por Candida albicans y exacerbación por efecto del estrés

RENNA MS; PORPORATTO C; AOKI MP; SALIDO RENTERIA B; CORREA SG; SOTOMAYOR CE

Mar del Plata

Congreso; XLVII Reunión Científica de la Sociedad de Investigación Clínica y LI Reunión Científica de la Sociedad Argentina de Inmunología.; 2003

C. albicans is the leading cause of opportunistic fungal infections in immunocompromised individuals. The liver is the first barrier controlling the hematogenous dissemination of C. albicans of intestinal origin, limiting the fungal growth and mounting an efficient inflammatory reaction that is crucial in the outcome of the infection; meanwhile the activation of pathogen virulence factors promote the tissue damage and the persistence in the host. In ours laboratory we developed an experimental model of immunosuppression by strees and micotic infection by study the role of the liver in the fungal infecton. Rats exposed simultaneously to C. albicans infection and chronic varied strees show alterations in innate immunity mediators associated with clear signs of hepatotoxicity. Here we evaluate the occurrence of apoptosis in situ and assess fungal infectivity under normal and stress conditions. Wistar rats were: untreated, stressed, C. albicans infected (Ca) and infected-stressed (Ca-S). After 3 days liver were obtained. In situ apoptosis was assessed by DAPI and TUNEL reaction; the local espression of TNF-a mRNA was determined by RT-PCR. Fungal infectivity was evaluated by histological studies. A novel and interestingly finding was the induction of apoptosis in situ during C. albicans infection (DAPI+ hepatocytes) and the increase of this phenomenon after stress exposures (TUNEL+ cell Ca vs CaS p<0,05). Cytokines like TNF-a  and Fas-FasL interaction are involve in hepatic injury and apoptosis induction. The expression of TNF-a mRNA was similar in both groups of infected animals. FasL expression, analyzed by flow cytometer in intrahepatic lymphocytes, was associated with fungal presence. This results show that  intrahepatic apoptosis is an early mechanism in the infections of C. albicans. This phenomenon was more severe after stress exposure.