Dectin-1-Mediated Production of Pro-Inflammatory Cytokines Induced by Yeast β-Glucans in Bovine Monocytes.

Ana R V Pedro,Tânia Lima,Margarida R G Maia,Alexandra Correia,Bárbara Leal,Elisabete G Martins,Manuel Vilanova,António J M Fonseca,Ricardo Fróis-Martins,Ana R J Cabrita,Isabel C Ramos

doi:10.3389/fimmu.2021.689879

Abstract

Yeast-derived products containing β-glucans have long been used as feed supplements in domesticated animals in an attempt to increase immunity. β-glucans are mainly recognized by the cell surface receptor CLEC7A, also designated Dectin-1. Although the immune mechanisms elicited through Dectin-1 activation have been studied in detail in mice and humans, they are poorly understood in other species. Here, we evaluated the response of bovine monocytes to soluble and particulate purified β-glucans, and also to Zymosan. Our results show that particulate, but not soluble β-glucans, can upregulate the surface expression of costimulatory molecules CD80 and CD86 on bovine monocytes. In addition, stimulated cells increased production of IL-8 and of TNF, IL1B, and IL6 mRNA expression, in a dose-dependent manner, which correlated positively with CLEC7A gene expression. Production of IL-8 and TNF expression decreased significantly after CLEC7A knockdown using two different pairs of siRNAs. Overall, we demonstrated here that bovine monocytes respond to particulate β-glucans, through Dectin-1, by increasing the expression of pro-inflammatory cytokines. Our data support further studies in cattle on the induction of trained immunity using dietary β-glucans.

Highlights

Immune modulation by natural compounds has long been studied in domesticated animals such as poultry, fish, and livestock, to enhance immunity and improve animal welfare and wellbeing, reducing the incidence of disease and the overuse of pharmaceutical compounds, such as antibiotics
Yeast b-glucans are usually composed of linear molecules of D-glucose units linked by b-1,3 glycosidic bonds with b-1,6 branching [8, 9]. b-glucans are recognized by immune cell surface pattern recognition receptors (PRR) such as C-type lectin domain family 7 member A (CLEC7A), designated as Dectin-1, complement receptor-3 (CR3), scavenger receptors, and lactosylceramide [10]
Cytokine production and mRNA expression were affected by treatment (P

Summary

Introduction

Immune modulation by natural compounds has long been studied in domesticated animals such as poultry, fish, and livestock, to enhance immunity and improve animal welfare and wellbeing, reducing the incidence of disease and the overuse of pharmaceutical compounds, such as antibiotics. B-glucans are recognized by immune cell surface pattern recognition receptors (PRR) such as C-type lectin domain family 7 member A (CLEC7A), designated as Dectin-1, complement receptor-3 (CR3), scavenger receptors, and lactosylceramide [10]. Biological activities of b-glucans depend on their recognition and downstream cell signalling, which in turn depend largely on the structure, conformation, and physical properties of the different b-glucans [9, 15]. Both particulate and soluble b-glucans bind Dectin-1, only the particulate form can induce Dectin-1 signalling and generate a “phagocytic synapse” [16]. Activation of Dectin-1 triggers an intracellular signalling cascade eliciting phagocytosis, production of cytokines, and reactive-oxygen species (ROS) [14,15,16,17,18,19]

Methods

Results

Conclusion