HEPATIC MONONUCLEAR CELLS (HMC) AND NKT CELLS SUBPOPULATION INVOLVED IN THE IMMUNE RESPONSE TO Candida albicans AND IN THE ABROGATION OF INTRAHEPATIC TOLERANCE.

RENNA, MARIA SOL; FIGUEREDO, CARLOS MAURICIO; RODRÍGUEZ-GALÁN, MARIA CECÍLIA; ICELY, PAULA; CORREA, SILVIA GRACIELA AND SOTOMAYOR CLAUDIA ELENA

BUENOS AIRES

Congreso; 14. 1º Congreso Franco Argentino de Inmunología; 2010

SOCIEDAD ARGENTINA INMUNOLOGIA

The liver is an organ that favours the induction of tolerance rather than the induction of immunity. Here we explored the contribution of total HMC and the NKT cell subpopulation in the balance of inflammatory/antiinflamatory mediators at local level during C.albicans primary infection and NKT cells activation. To this end, HMC purified from control (N) and infected (Ca) animal (day 1), were incubated 24h with or without the fungus(1:1). C.albicans primary infection clearly induces INFg production by HMC (25.5±6.4 fold increase vs N-HMC production, p<0.05) while the release of tolerogenic cytokines such as IL-10 (302±32 pg/ml) and TGFb (158±23 pg/ml) remained unmodified. After a second in vitro contact with the fungus, the HMC showed an increase in INFg production (62±6.5 fold increase vs N-HMC production, p<0.05) and no significant changes in the production of tolerogenic cytokines. NKT cells play a key role in the regulation of infectious diseases due to its ability to produce INFg and/or IL-4. NKT cells purified from infected livers (cell sorting) were able to release higher concentrations of INFg (100±10pg/mL, p<0.05) and very low levels of IL-4 (1.2±0.2pg/mL). Moreover, after in vitro reexposure to the pathogen, the INFg production increased significantly (340±15pg/mL, p<0.05), while IL-4 concentration was unmodified. When intrahepatic NKT cells sorted out of uninfected controls were cultured in the absence of any stimuli, we detected very low levels of IL-4 and absence of INFg production. The basal production of these cytokines was not affected after the challenge in vitro with the fungus, suggesting the need of antigen presenting cells (APC) in NKT cells activation. Co-cultures of the fungus with CD11b/c-depleted N-HMC cells confirmed these results. These findings show that C.albicans hepatic colonization breaks liver tolerance, with the direct involvement of NKT cells. The presence of local APC could be necessary for the activation of these lymphocytes.