lipoteichoic-acid and Bronchial-Hyperreactivity

Sublingual immunotherapy (SLIT) has been established in humans as a safe and efficacious treatment for type I respiratory allergies.. In this study, we compared three Toll-like receptor (TLR) 2 ligands (Pam3CSK4, Porphyromonas gingivalis lipopolysaccharide and lipoteichoic acid) as potential adjuvants for sublingual allergy vaccines.. These molecules were tested in co-cultures of adjuvant-pre-treated dendritic cells (DCs) with murine naïve CD4(+) T lymphocytes. Patterns of cytokine production, phenotype, proliferation and gene expression were analysed by ELISA, cytofluorometry and quantitative PCR, respectively. TLR2 ligands were subsequently tested in a model of SLIT in BALB/c mice sensitized with ovalbumin (OVA).. Among the three TLR2 ligands tested, the synthetic lipopeptide Pam3CSK4 is the most potent inducer of IL-12p35 and IL-10 gene expression in murine bone marrow-derived DCs, as well as in purified oral myeloid DCs. Only Pam3CSK4-treated DCs induce IFN-gamma and IL-10 secretion by naïve CD4(+) T cells. Sublingual administration of Pam3CSK4 together with the antigen in BALB/c mice sensitized to OVA decreases airway hyperresponsiveness as well as OVA-specific T-helper type 2 (Th2) responses in cervical lymph nodes dramatically.. Pam3CSK4 induces Th1/regulatory T cell responses, and as such, is a valid candidate adjuvant for sublingual allergy vaccines.

Topics: Adjuvants, Immunologic; Administration, Sublingual; Animals; Antigen Presentation; Asthma; Bronchial Hyperreactivity; CD4-Positive T-Lymphocytes; Cytokines; Dendritic Cells; Desensitization, Immunologic; Gene Expression; Humans; Interferon-gamma; Interleukin-10; Lipopeptides; Lipopolysaccharides; Lymph Nodes; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Ovalbumin; Porphyromonas gingivalis; T-Lymphocytes, Helper-Inducer; Teichoic Acids; Toll-Like Receptor 2