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

作者:Sol Renna Maria; Mauricio Figueredo Carlos; Cecilia Rodriguez Galan Maria; Alejandra Icely Paula; Peralta Ramos Javier Maria; Graciela Correa Silvia; Elena Sotomayor Claudia
来源:International Immunology, 2012, 24(5): 315-325.
DOI:10.1093/intimm/dxs001

摘要

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 CD3+, NK+ and NKT+ intrahepatic lymphoid subsets and 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-beta and IL-4 was severely modified upon the robust IFN-gamma 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 to activate tolerogenic NKT cells from naive animals. In vitro experiments performed with HMC cells depleted of the CD11b/c+ population revealed that in the absence of APC, NKT cells are unable to produce IFN-gamma 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.

  • 出版日期2012-5