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Wonbeom Paik, Francis Alonzo, Katherine L Knight, Probiotic exopolysaccharide protects mice from acute Staphylococcus aureus bloodstream infection, reducing bacterial burden and limiting inflammation, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 190.47, https://doi.org/10.4049/jimmunol.202.Supp.190.47
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Abstract
Staphylococcus aureus causes severe systemic infection with high mortality. We previously showed that the probiotic Bacillus subtilis, produces an exopolysaccharide (EPS) that induces anti-inflammatory M2 macrophages. We used a lethal S. aureus bloodstream infection model, and found that mice treated with EPS prior to infection survived, and had reduced bacterial burden in the liver and spleen, as well as reduced levels of inflammatory cytokines. We showed that the EPS-induced M2 macrophages inhibited the growth of S. aureus in vitro, and by using an inhibitor of reactive oxygen species (ROS), we found that the growth inhibition of S. aureus was mediated by ROS, an M1-like property. However, these macrophages retained the M2-like capacity to inhibit proinflammatory activation of T cells by S. aureus superantigen. To test if the reduction in proinflammatory cytokines in EPS-treated mice during infection is due to anti-inflammatory effects of EPS rather than to the reduced bacterial load, we isolated splenocytes from EPS-treated mice and stimulated them with S. aureus ex vivo. We found that levels of IFN-γ, KC, and IL-6 were decreased, whereas the production of IL-10 was increased, indicating that the decrease in inflammation by EPS is not solely due to reduction in bacterial load. We suggest that the EPS-induced M2 macrophages represent “hybrid” macrophages capable of both M1- and M2-like functions and could be used to protect hosts from lethal S. aureus infection by bolstering anti-bacterial immunity, while simultaneously limiting inflammation.
