Multiple Sclerosis-associated Bacterial Ligand 654

Background and Aims. 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- 0 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. Materials and Methods. HMC3 human microglial cells were treated with IFN- 0 or Fingolimod. Cytokine secretion was evaluated using a multiplex system, and microglia polarization was assessed by flow cytometry.Results. We observed that treatment with IFN- 0 or Fingolimod induced differential secretion of various pro-inflammatory cytokines. Upon cell stimulation with Lipid 654, we observed that IFN- 0 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.Conclusions. Our findings provide new clues of still unknown mechanisms of action of IFN- 0 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. (c) 2021 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.

Automated summary

This study aimed to investigate the cellular response of human microglial cells to the first-line medications IFN-β and Fingolimod for multiple sclerosis (MS) management, and determine their effects on the cells' response to an MS-associated bacterial ligand, Lipid 654. The results showed that the medications induced differential secretion of pro-inflammatory cytokines and decreased the secretion of M1-associated cytokines when the cells were stimulated with Lipid 654. These findings provide new insights into the mechanisms of action of these medications in human microglia and their potential use in regulating the inflammatory response in MS.