Acetylcholine protects against Candida albicans infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

Ranjith Rajendran, Elisa Borghi, Monica Falleni, Federica Perdoni, Delfina Tosi, David F. Lappin, Lindsay O’Donnell, Darren Greetham, Gordon Ramage, Christopher Nile

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)834-844
Number of pages11
JournalEukaryotic Cell
Volume14
Issue number8
Early online date19 Jun 2015
DOIs
Publication statusPublished - 1 Aug 2015
Externally publishedYes

Fingerprint

Hemocytes
Biofilms
Candida albicans
Acetylcholine
Infection
Mycoses
Gentian Violet
Microarray Analysis
Muramidase
Bacterial Infections
Larva
Real-Time Polymerase Chain Reaction
Immunity
Histology

Cite this

Rajendran, Ranjith ; Borghi, Elisa ; Falleni, Monica ; Perdoni, Federica ; Tosi, Delfina ; Lappin, David F. ; O’Donnell, Lindsay ; Greetham, Darren ; Ramage, Gordon ; Nile, Christopher. / Acetylcholine protects against Candida albicans infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model. In: Eukaryotic Cell. 2015 ; Vol. 14, No. 8. pp. 834-844.
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Acetylcholine protects against Candida albicans infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model. / Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F.; O’Donnell, Lindsay; Greetham, Darren; Ramage, Gordon; Nile, Christopher.

In: Eukaryotic Cell, Vol. 14, No. 8, 01.08.2015, p. 834-844.

Research output: Contribution to journalArticle

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