β-Glucan-Induced IL-10 Secretion by Monocytes Triggers Porcine NK Cell Cytotoxicity.

Leen Hermans,Sofie Denaeghel,Steffi De Pelsmaeker,Herman W Favoreel,Bert Devriendt,Eric Cox

doi:10.3389/fimmu.2021.634402

Abstract

Beta-glucans are naturally occurring polysaccharides present in cell walls of fungi, yeast, bacteria, cereals, seaweed, and algae. These microbe-associated molecular patterns (MAMPs) possess immunomodulatory properties. In human, it has been suggested that NK cells can be activated by β-glucans. Here, we aimed to elucidate whether β-glucans modulate porcine NK cell responses in vitro and if so, how these effects are mediated. We investigated the effect of two β-glucans, Macrogard and Curdlan, which differ in solubility and structure. Direct addition of β-glucans to purified porcine NK cells did not affect cytotoxicity of these cells against K562 target cells. However, when using PBMC instead of purified NK cells, β-glucan addition significantly increased NK cell-mediated cytotoxicity. This effect depended on factors secreted by CD14+ monocytes upon β-glucan priming. Further analysis showed that monocytes secrete TNF-α, IL-6, and IL-10 upon β-glucan addition. Of these, IL-10 turned out to play a critical role in β-glucan-triggered NK cell cytotoxicity, since depletion of IL-10 completely abrogated the β-glucan-induced increase in cytotoxicity. Furthermore, addition of recombinant IL-10 to purified NK cells was sufficient to enhance cytotoxicity. In conclusion, we show that β-glucans trigger IL-10 secretion by porcine monocytes, which in turn leads to increased NK cell cytotoxicity, and thereby identify IL-10 as a potent stimulus of porcine NK cell cytotoxicity.

Highlights

Beta-glucans are naturally occurring glucose polymers that are important structural components of the cell wall of e.g., fungi, yeast, bacteria, cereals, seaweed, and algae [1]
One report suggested a direct effect of barley β-1,3/1,4-glucans on human Natural Killer (NK) cell cytotoxicity toward K562 cells [20]
Another study claimed that both zymosan and a particulate yeast β-1,3-glucan showed a direct and dose-dependent inhibition of human NK cell cytotoxicity

Summary

INTRODUCTION

Beta-glucans are naturally occurring glucose polymers that are important structural components of the cell wall of e.g., fungi, yeast, bacteria, cereals, seaweed, and algae [1]. Β-glucans enhance the phagocytotic capacity of macrophages [8] and oxidative burst of monocytes, macrophages and neutrophils [3, 9,10,11] They induce proliferation of peripheral blood mononuclear cells (PBMC) in vitro [11] and stimulate macrophages and dendritic cells to produce cytokines and chemokines, including TNF-α [11, 12], IL-12 [12], CXCL2, IL6 [13], IL-1β, and IL-10 [11]. MHC class I on the cell surface delivers a potent inhibitory signal to NK cells, and MHC class I downregulation on malignant cells or virus-infected cells contributes to NK cell activation and killing of these target cells [19] This mechanism is exploited to investigate NK cell-mediated cytotoxicity in in vitro assays, in which cell lines expressing limited amounts of MHC class I, such as K562, are co-cultured with effector cells. Since administration of β-glucans in vivo is generally not accompanied by side effects [14], further insights into NK cell modulation by β-glucans may yield important information with regard to the use of βglucans in animal husbandry, and pave the way toward new strategies in vaccine development, anti-viral therapies and possibly cancer therapies

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT