Candida albicans activation of human monocytes toward M2 profile is reversed by Amphotericin B and Fluconazole

Abstract

Phagocytes, including monocytes/macrophages, play an important role in thehost defense during Candida albicans infections. In the L-arginine metabolism,the balance between the activation of two enzymes, inducible Nitric OxideSynthase (iNOS) and arginase, promotes in the macrophages two alternativemetabolic states, while M1 profile is related with host protection, M2 favored thefungal growth and evasion. Our aim was to evaluate the effect of AmphotericinB (AMB) and Fluconazole (FLC) on polarization of human monocytes to M2profile induced by C. albicans. The human monocytic (Mo) cell line U937 wasco-cultured with viable yeast of C. albicans, or Lipopolysaccharides (LPS) orPhorbol-12-myristate-13-acetate (PMA). Nitric Oxide (NO), cytokines productionand arginase activity were evaluated. The effect of AMB or FLC on thesemetabolic pathways in immune cells and on fungus intrinsic arginase activitywas studied. C. albicans inhibits NO production in human-monocyte and inducesstrong host arginase activity (p<0.0001). AMB and FLC inhibited C. albicansinducedarginase activity in immune cells (p<0.001), reaching a percentage ofinhibition of 90% for AMB and 78% for FLC. Arginase intrinsic activity of thefungus was blocked by nor-NOHA (arginase inhibitor) and AMB (p<0.05). Theseresults show that C. albicans drives human Mo toward M2 profile and that bothantifungal drugs evaluated have the ability to revert C. albicans-induced M2profile. In a relevant manner, it also provides data about additional effect of AMBas inhibitor of C. albicans endogenous arginase activity. Here in we providenew evidence for the effect of these drugs over the immune cells and the yeast.