Sub-cytotoxic Concentration of AflatoxinB2 Prevents NO-Mediated Increased Mitochondrial Membrane Potential and Intracellular Killing of Candida albicans in Macrophages Running Title: Changes of Nitric Oxide and Mitochondrial Membrane Potential by Aflatoxin

Aflatoxin B2 (AFB2) is a carcinogenic and immunotoxic metabolite produced by Aspergillus flavus growing on crops and food. The immune functions of rat macrophages when exposed to sub-cytotoxic concentrations of AFB2 which may make exposed people susceptible to Candida albicans infections, have been assessed. This level of AFB2 significantly prevents immune functions of macrophages by inhibiting nitric oxide (NO) production, mitochondrial membrane potential and intracellular killing of C.albicans by macrophages even in the presence of activating signal, interferon-γ. AFB2-induced prevention of increased membrane potential and intracellular killing of C.albicans by macrophages may be due to the prevention of iNOS (inducible nitric oxide synthetase) activity which results in the suppression of NO production. This study provides an important clue to the possibility that macrophages may give refuge to C.albicans for survival and dissemination and thus C.albicans is capable of inducing self-protective effect by the action of AFB2. The presence of AFB2 would thus help the macrophages to allow the C.albicans to replicate and persist, while being invisible to the immune system. This plausibility will give impetus to medicinal development.