Binding of soluble yeast β-1,3/1,6 glucans to complement receptors leads to immunomodulatory effects on both innate and adaptive human immune cells (55.8)

Abstract

Abstract β-glucans are considered as fungal pathogen-associated molecular patterns (PAMPs) that are recognized by cells of the human innate immune system. Few studies have focused on recognition and immunostimulatory functions of soluble β-glucan (sβG) on innate and adaptive human immune cells. In this study, we investigated recognition and immunomodulatory functions of an analytically well-characterized form of yeast-derived sβG by human neutrophils, monocytes, and B-cells. Binding studies demonstrated that the sβG bound to human neutrophils and monocytes via complement receptor 3 (CR3) and B-cells via CR2, and that receptor binding was complement-dependent. Opsonization of soluble β-glucan was detected by the presence of complement protein, iC3b on β-glucan-bound cells. Binding of sβG on human neutrophils resulted in enhanced directed migration of neutrophils towards IL-8. In the presence of other PAMPs (eg, LPS), binding of sβG was increased on both neutrophils and monocytes. Interestingly, when sβG was combined with either a TLR7/8 agonist (imidazoquinoline CL097) or a TLR9 agonist (CpG oligonucleotide, CpG 2006), enhanced activation of B-cells was observed as measured by B cell proliferation. These results demonstrate for the first time that complement opsonization of sβG makes it amenable not only for recognition by several complement receptors, but also modulation of immune functions of both innate and adaptive immune cells.