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

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.

β-Glucans from Trametes versicolor (L.) Lloyd Is Effective for Prevention of Influenza Virus Infection

“…In this study, our data suggested that β-glucan induces IL-10 expression and reduces virus-induced lung pathological inflammation in experimental animals. In addition, a recent study reported that β-glucan enhances NK cell killing activity by promoting IL-10 secretion by porcine monocytes [33], which suggests that IL-10 indirectly regulates NK killing function and improves antiviral effects. However, β-glucan inhibition of virus-infected lung injury may involve multiple mechanisms, and this protective mechanism will be revealed using gene deletion animal models in the future.…”

Comparative transcriptomics of porcine liver-resident CD8αdim, liver CD8αhigh and circulating blood CD8αhigh NK cells reveals an intermediate phenotype of liver CD8αhigh NK cells

“…multiple days are performed in a basal medium containing rhIL-15 to assure NK cell viability (60). In however, rpIL-15 is not sufficient retain satisfying viability in NK cells and TGF-b treatment was therefore combined with either IL-2 or IL-10, cytokines that are able to maintain porcine cNK cell viability (61,62). In line with a report in human (58), IL-10 nor TGF-b were able to increase Eomes expression in porcine cNK cells, but TGF-b was able to downregulate T-bet expression in these cells.…”

An important polysaccharide from fermentum

“…Natural killer cells (NK cells) are extremely important immune cells in the body, which are naturally occurring non-specific immune killer cells in the organism and play a crucial role in intracellular immune processes against parasitic infections, tumours and viruses, and have both immunomodulatory and cytotoxic functions. In an in vitro experiment to investigate how Fermentum β-polysaccharide activates porcine NK cells, the addition of β-polysaccharide to porcine NK cells triggered the release of cytokines TNF-α, IL-6 and IL-10 from peripheral blood mononuclear cells ( Hermans et al, 2021 ). Increased NK cytotoxicity can mediate the killing of tumour cells and virus-infected cells, thus enhancing the non-specific immune function of the body.…”