Candida albicans β-Glucan Differentiates Human Monocytes Into a Specific Subset of Macrophages

• Published in: Frontiers in immunology Vol. 9; p. 2818
• Main Authors: Leonhardt, Julia, Große, Silke, Marx, Christian, Siwczak, Fatina, Stengel, Sven, Bruns, Tony, Bauer, Reinhard, Kiehntopf, Michael, Williams, David L, Wang, Zhao-Qi, Mosig, Alexander S, Weis, Sebastian, Bauer, Michael, Heller, Regine
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 30.11.2018
• Subjects: Autocrine Communication - drug effects; Autocrine Communication - immunology; beta-Glucans - chemistry; beta-Glucans - pharmacology; Candida albicans; Candida albicans - chemistry; Cell Differentiation - drug effects; Cell Differentiation - immunology; Humans; Immunology; Macrophage Colony-Stimulating Factor - immunology; Macrophages - cytology; Macrophages - immunology; Male; monocyte survival; monocyte to macrophage differentiation; Monocytes - cytology; Monocytes - immunology; Paracrine Communication - drug effects; Paracrine Communication - immunology; trained immunity; β-glucan; Candida albicans; β-glucan; monocyte to macrophage differentiation; trained immunity; monocyte survival
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.02818

β-Glucan derived from cell walls of 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.