Adjuvant effects of peptidoglycan on CD4 +T cell activation by MHC-II +fibroblast-like synoviocytes

Abstract Lyme arthritis (LA) is the predominant late-stage manifestation of disease, caused by tick-borne spirochete Borrelia burgdorferi. LA can resolve with antibiotic therapy or persist after treatment in a subset patients, known as post-antibiotic LA. Post-antibiotic characterized proliferative synovitis, dysregulated Th1/ IFNɣ responses and MHC-II+ fibroblast-like synoviocytes (FLS), common cell type inflamed joints. High levels B. burgdorferi peptidoglycan (PG) have been found patient synovia, yet effects PG on host immune are not well characterized. We hypothesize that acts an adjuvant to enhance antigen presentation CD4 +T activation joint. To test this, primary murine macrophages FLS, both abundant were treated vitro IFNɣ, PG, both. Stimulation led upregulation MHC-II IFNɣ-dependent manner, expected. FLS stimulated production proinflammatory cytokines, which was enhanced muramyl-dipeptide subunit NOD2 ligand. examine T responses, IFNɣ-primed +FLS co-cultured OT-II mouse cells (all identical antigen-specific receptors) supplemented cognate OVA 323–339peptide. activated naïve proliferation, stimulation. Co-culture supernatants showed upregulated IL-12 production, indicating Th1 response. Negative controls using alternative 257–264peptide NOD2-deficient failed induce responses. These data show enhancing peptide-specific +FLS.