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Updated: Oct 10, 2025
Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Multiple Sclerosis-associated Bacterial Ligand 654
Jordan Brown1, Colleen Everett1, Jose A Barragan1
1Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA.
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-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.
Materials And Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Interferon-beta (IFN-β) and Fingolimod treatments modulate microglial responses to bacterial ligands, potentially revealing new therapeutic mechanisms for multiple sclerosis (MS). These MS drugs reduce pro-inflammatory cytokine secretion and M1 polarization in human microglia.
Area of Science:
- Neuroimmunology
- Microbiology
Background:
- Multiple sclerosis (MS) pathogenesis involves complex risk factors, with emerging evidence implicating microbiome-derived ligands.
- Human microglia play a critical role in neuroinflammation within the central nervous system.
Purpose of the Study:
- To investigate the effects of first-line MS medications, Interferon-beta (IFN-β) and Fingolimod, on human microglial cellular responses.
- To determine if these treatments alter microglial reactivity to Lipid 654, a bacterial ligand associated with MS.
Main Methods:
- Human microglial cells (HMC3) were treated with IFN-β or Fingolimod.
- Cytokine secretion was quantified using multiplex assays.
- Microglia polarization was assessed via flow cytometry.
Main Results:
- IFN-β and Fingolimod induced differential pro-inflammatory cytokine secretion.
- Both treatments reduced M1-associated cytokine secretion upon stimulation with Lipid 654.
- Flow cytometry indicated that IFN-β and Fingolimod contained the M1 microglial phenotype post-Lipid 654 stimulation.
Conclusions:
- Findings offer novel insights into the mechanisms of IFN-β and Fingolimod in human microglia.
- These results suggest potential new therapeutic strategies for regulating inflammatory responses in MS.
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