Abstract Details

Title Human Gut-Derived Commensal Bacterium Suppresses Neuroinflammation via Microbe-Associated Molecular Patterns

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 9-003

Objective Given that Lactobacillus paracasei (Lb) is sufficient to ameliorate experimental autoimmune encephalomyelitis (EAE), a preclinical model of central nervous system (CNS) autoimmune disease, we sought to elaborate the mechanisms behind this beneficial host-microbe interaction.

Background An emerging area of research in the multiple sclerosis (MS) field is the study of commensal microbes that may affect disease initiation and progression. We have previously identified a significant negative correlation between the relative abundance of Lactobacillus and the severity of EAE, mirroring what is seen in MS patients, and we demonstrated that human gut-derived Lb is sufficient to suppress EAE.

Design/Methods To induce EAE, we immunized C57BL/6 mice with myelin oligodendrocyte glycoprotein. Mice were treated daily via oral gavage with live Lb, heat-killed Lb, or vehicle and disease severity was compared between treatments. Disease severity was determined using a symptom scoring system and immunohistochemistry for CNS demyelination. CNS flow cytometry and serum chemokine profiling were performed at various points during disease.

Results Surprisingly, in wild type mice we found that heat-killed Lb was as effective as live Lb in protecting animals against EAE, as measured by disease score and demyelination. By flow cytometry, we observed that heat-killed Lb-treated animals had reduced numbers of CNS-infiltrating leukocytes and this was associated with a decrease in the chemokines CCL3, CCL4, CXCL5, and CXCL13 in the serum, all of which are involved in leukocyte migration. Given the protective effect of heat-killed Lb, we assessed whether host Toll-like receptor 2 (TLR2), which senses major components of the Lb cell wall, was necessary for protection. The benefit of Lb in EAE was abrogated in TLR2-deficient mice.

Conclusions Our results suggest that Lb suppresses CNS autoimmune disease predominantly through Lb-associated molecular patterns recognized by host TLR2 to suppress chemokine signaling and subsequent leukocyte infiltration into the CNS.

Authors/Disclosures
John Michael Sanchez (University of Utah) PRESENTER	Mr. Sanchez has nothing to disclose.
	No disclosure on file
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