The yeast quorum sensing molecule, farnesol, acts as an adjuvant to promote innate inflammatory responses (VAC8P.1060)

Abstract

Abstract Candida albicans is a polymorphic fungus that can cause systemic disease in immunocompromised and transplant patients, but is maintained as a commensal in healthy adults mainly through the actions of innate immunity. At low cell density, C. albicans secretes the quorum-sensing molecule, farnesol (FOH) which acts as a virulence factor. Our previous work indicates that FOH alone promotes chemotaxis of macrophages (MΦ) and synergizes with the TLR-2 agonist zymosan to promote MΦ cytokine secretion in vitro. We next determined whether FOH could act similarly to promote inflammatory responses in vivo. After intra-peritoneal injection, FOH increased the numbers of MΦ and neutrophils in the peritoneal cavity compared to untreated or thioglycollate treated mice. FOH treatment increased IL-6 and CCL2 mRNA in peritoneal exudate cells consistent with MΦ activation. In addition, cell surface expression of MHC class II and co-stimulatory molecules on dendritic cells in the peritoneum were higher in FOH injected mice compared to controls, suggesting FOH may prime antigen presenting cells for T cell activation. Currently we are investigating whether FOH can act as an adjuvant to promote antigen specific, cell mediated or antibody mediated immunity or a combination of both types. Defining the immunostimulatory properties of FOH, a potentially novel adjuvant, will improve strategies for vaccine design that promotes robust immunity against a variety of infectious diseases.