Multiple Sclerosis-associated Bacterial Ligand 654

Abstract

Many endogenous and exogenous risk factors are associated with multiple sclerosis (MS), but recent studies suggest that microbiome-derived ligands, play a role in the disease process. The goal of this study was to characterize the cellular response elicited in human microglia upon treatment with IFN-β and Fingolimod, two first line medications for the management of MS, and determine whether these treatments affect the response of microglial cells to an MS-associated bacterial ligand, Lipid 654. HMC3 human microglial cells were treated with IFN-β or Fingolimod. Cytokine secretion was evaluated using a multiplex system, and microglia polarization was assessed by flow cytometry. We observed that treatment with IFN-β or Fingolimod induced differential secretion of various pro-inflammatory cytokines. Upon cell stimulation with Lipid 654, we observed that IFN-β and Fingolimod decreased the secretion of M1-associated cytokines. Using flow cytometry, we observed that the decrease in inflammatory cytokine secretion was likely due to a containment of M1 phenotype of microglia after stimulation with Lipid 654. Our findings provide new clues of still unknown mechanisms of action of IFN-β and Fingolimod in human microglia, which will prompt new avenues of research on the use of these therapies in the regulation of the inflammatory response in MS.