Abstract
β-Glucan derived from cell walls of Candida albicans is a potent immune modulator. It has been shown to induce trained immunity in monocytes via epigenetic and metabolic reprogramming and to protect from lethal sepsis if applied prior to infection. Since β-glucan-trained monocytes have not been classified within the system of mononuclear phagocytes we analyzed these cells metabolically, phenotypically and functionally with a focus on monocyte-to-macrophage differentiation and compared them with naïve monocytes and other types of monocyte-derived cells such as classically (M1) or alternatively (M2) activated macrophages and monocyte-derived dendritic cells (moDCs). We show that β-glucan inhibits spontaneous apoptosis of monocytes independent from autocrine or paracrine M-CSF release and stimulates monocyte differentiation into macrophages. β-Glucan-differentiated macrophages exhibit increased cell size and granularity and enhanced metabolic activity when compared to naïve monocytes. Although β-glucan-primed cells expressed markers of alternative activation and secreted higher levels of IL-10 after lipopolysaccharide (LPS), their capability to release pro-inflammatory cytokines and to kill bacteria was unaffected. Our data demonstrate that β-glucan priming induces a population of immune competent long-lived monocyte-derived macrophages that may be involved in immunoregulatory processes.
Highlights
Candida albicans β-1-3,1-6-glucan (β-glucan), a pathogen-associated molecular pattern (PAMP) present in the fungal cell wall, has been characterized as a potent immune modulator
We show that β-glucan inhibits spontaneous apoptosis of monocytes independent from autocrine or paracrine macrophage colony-stimulating factor (M-CSF) release and stimulates monocyte differentiation into macrophages. β-Glucan-differentiated macrophages exhibit increased cell size and granularity and enhanced metabolic activity when compared to naïve monocytes
We show that transient treatment of monocytes with β-glucan inhibits spontaneous apoptosis and stimulates long-term differentiation into a specific subset of immune competent macrophages
Summary
Candida albicans β-1-3,1-6-glucan (β-glucan), a pathogen-associated molecular pattern (PAMP) present in the fungal cell wall, has been characterized as a potent immune modulator. Β-Glucan is the best characterized stimulus to induce trained immunity in monocytes. The classification of trained monocytes remains enigmatic [8] This is underlined by the heterogeneous terminology, referring to β-glucan-trained cells as “trained monocytes” [6, 9], “memory macrophages” [8], “trained macrophages” [7, 10] or “circulating differentiated monocytes” [4]. Β-Glucan-treated monocytes were compared with classically (M1-like) and alternatively activated (M2like) monocyte-derived macrophages and monocyte-derived dendritic cells (moDCs) with respect to metabolism, phenotype and function. Our data show that β-glucan protects monocytes from spontaneous apoptosis and promotes differentiation into a specific subset of metabolically highly active macrophages, which exhibit an M2-like surface marker profile. Our data show that β-glucan protects monocytes from spontaneous apoptosis and promotes differentiation into a specific subset of metabolically highly active macrophages, which exhibit an M2-like surface marker profile. β-Glucandifferentiated macrophages are able to kill live bacteria and to respond to LPS with secretion of proinflammatory cytokines and with an increased release of IL-10
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