Differential hepatic damage between immunocompetent and immunosuppresed host during Candida albicans infection: contribution of early mediators and intrahepatic lymphocyte recruitment.

RENNA MS; FIGUEREDO CM; CORREA SG; RIERA CM; SOTOMAYOR CE

Río de Janeiro. Brasil.

Congreso; 13 th Internacional Congress of Immunology; 2007

ALAI

The liver constitutes the first barrier in the control of hematogenous dissemination from Candida albicans from intestinal origin. When rats infected with C.albicans(Ca group) are exposed to chronic-varied-stress (CaS group), the early inflammatory response is compromised and the infection evolution is more severe. In both groups the fungal burden is associated with hepatotoxicity, steatosis, increment of hepatic enzymes and lipid peroxidation; interestingly, stress mediators exacerbated these changes. We demonstrated that during C.albicans infection, a marked hepatocyte apoptosis was observed, and the highest level of cell death was in CaS animals. Herein, we studied possible mediators involved in the differential liver damage observed between the groups.  We founded a significantly higher hepatic level of TNF-a mRNA transcripts during two days(D) post infection. On D3 transient expression of TNF-a was observed only in Ca group. The expression of Fas protein remained invariant in hepatocytes but the Fas-L molecule expressed on infiltrating liver cells was markedly increased after the infection and similar in both groups. The hepatic lymphocyte compartment may be involved in protection/injury mechanisms. We purified and characterized the intrahepatic CD3+, NK+ and NKT+ cells and we studied the hepatic cytokine network involved in the cell recruitment. The number of CD3+, NK+ and NKT+ cells increased early after C.albicans infection, unlike the kinetic profile of certain proinflammatory cytokines(IL-6) and chemokines(CCL-4, CXCL-8) was different after neuroendocrine products exposition. In the complex scenario of early liver injury in stress-immunosuppressed host these parameters evaluated cannot fully explain the major hepatic damage observed in these animals.