title: Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model.
abstract: 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.
authors.affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Ranjith
authors.initials: R
authors.lastname: Rajendran
authors.affiliation: Laboratory of Microbiology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Borghi
authors.affiliation: Division of Human Pathology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Falleni
authors.affiliation: Laboratory of Microbiology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Perdoni
authors.affiliation: Division of Human Pathology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Delfina
authors.initials: D
authors.lastname: Tosi
authors.affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: David F
authors.initials: DF
authors.lastname: Lappin
authors.affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Lindsay
authors.initials: L
authors.lastname: O'Donnell
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom.
authors.forename: Darren
authors.initials: D
authors.lastname: Greetham
authors.affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Ramage
authors.affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom christopher.nile@glasgow.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nile
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D006434:Hemocytes / Q000187:drug effects*; D007814:Larva / Q000382:microbiology; D009036:Moths / Q000382:microbiology*
chemical_list: D000109:Acetylcholine