Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation
Lena K. Siewert, Kristina Berve, Elisabeth Pössnecker, Julia Dyckow, Amel Zulji, Ryan Baumann, Aida Munoz-Blazquez, Gurumoorthy Krishnamoorthy, David Schreiner, Sharon Sagan, Charlotte Nelson, Joseph J. Sabatino, Kazuki Nagashima, Médéric Diard, Andrew J. Macpherson
TL;DR
This study shows how gut bacteria expressing brain antigens can trigger immune responses linked to autoimmune neuroinflammation, like multiple sclerosis.
Contribution
The paper introduces a novel method of using genetically engineered gut bacteria to study antigen-specific immune activation in autoimmunity.
Findings
Bacteria expressing myelin peptides, but not ovalbumin, worsen autoimmune neuroinflammation in mice.
Antigen-specific T and B cells in the gut are activated by these engineered bacteria.
The findings suggest that targeting specific gut bacteria could help treat autoimmune diseases.
Abstract
Microbiome-based therapies are promising new treatment avenues. While global alterations in microbiota composition have been shown in multiple sclerosis, whether and how gut microbiota influence autoimmune responses in an antigen-specific manner is unclear. Here, we genetically engineered gut bacteria to express a brain antigen and dissect their pathogenic potential in a murine model of autoimmune neuroinflammation. Colonization with bacteria expressing myelin - but not ovalbumin-peptide exacerbates an encephalitogenic immune response in the gut by activating antigen-specific T cells as well as B cells leading to accelerated neuroinflammatory disease. These results demonstrate how antigen-specific microbial modulation can influence autoimmunity, providing insight for development of therapeutic strategies targeting specific bacterial taxa for treatment of MS and other autoimmune diseases.
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Taxonomy
TopicsGut microbiota and health · Vagus Nerve Stimulation Research · Multiple Sclerosis Research Studies