Abrogation of spontaneous liver tolerance during immune response to Candida albicans: contribution of NKT and hepatic mononuclear cells

. RENNA MS, FIGUEREDO CM, RODRÍGUEZ-GALÁN MC, ICELY PA, PERALTA RAMOS JM, CORREA SG, SOTOMAYOR CE.

INTERNATIONAL IMMUNOLOGY

OXFORD UNIV PRESS

Año: 2012 vol. 24 p. 315 - 325

0953-8178

Hepatic mononuclear cells (HMC) are a heterogeneous population with innate immune properties involved in the response to several pathogens. Herein, during the primary infection with Candida albicans, we observed dynamic changes in CD31, NK1 and NKT1 intrahepatic lymphoid subsets and 15 a significant increase in the absolute number of antigen-presenting cells (APC). The liver tolerogenic microenvironment sustained by higher levels of IL-10, transforming growth factor-b and IL-4 was severely modified upon the robust IFN-g production after the fungal colonization. NKT cells purified from infected animals released significant amounts of IFN-gamma and the production of this cytokine was exacerbated after a second contact with the fungus. Interestingly, C. albicans per se was unable 20 to activate tolerogenic NKT cells from naive animals. In vitro experiments performed with HMC cells depleted of the CD11b/c1 population revealed that in the absence of APC, NKT cells are unable to produce IFN-g in response to C. albicans. Our findings constitute the first evidence that this innate lymphocyte population is involved in the pathogenesis of C. albicans infection.