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

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 beta-glucans. Here, we aimed to elucidate whether beta-glucans modulate porcine NK cell responses in vitro and if so, how these effects are mediated. We investigated the effect of two beta-glucans, Macrogard and Curdlan, which differ in solubility and structure. Direct addition of beta-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, beta-glucan addition significantly increased NK cell-mediated cytotoxicity. This effect depended on factors secreted by CD14+ monocytes upon beta-glucan priming. Further analysis showed that monocytes secrete TNF-alpha, IL-6, and IL-10 upon beta-glucan addition. Of these, IL-10 turned out to play a critical role in beta-glucan-triggered NK cell cytotoxicity, since depletion of IL-10 completely abrogated the beta-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 beta-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.

Automated summary

The study showed that beta-glucans enhance NK cell cytotoxicity in pigs by inducing IL-10 secretion from monocytes, leading to increased cytotoxicity in NK cells in PBMC. IL-10 plays a critical role in beta-glucan-triggered NK cell cytotoxicity.