Both neuronal
acetylcholine and nonneuronal
acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of
acetylcholine in the pathogenesis of
bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of
acetylcholine in the pathogenesis of
fungal infections is unknown. Therefore, the aim of this study was to determine whether
acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans
infection. The effect of
acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a
crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans
infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella
infection model. In addition, its effect on modulation of host immunity to C. albicans
infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology,
lysozyme assays, hemolytic assays, and real-time PCR.
Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition,
acetylcholine protected G. mellonella larvae from C. albicans
infection mortality. The in vivo protection occurred through
acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore,
acetylcholine also inhibited
inflammation-induced damage to internal organs. This is the first demonstration of a role for
acetylcholine in protection against
fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore,
acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of
fungal infections.