title: The TLR2 agonists lipoteichoic acid and Pam3CSK4 induce greater pro-inflammatory responses than inactivated Mycobacterium butyricum.
abstract: The innate immune system can recognize pathogen-associated molecular patterns (PAMP) through toll-like receptors (TLRs). TLR stimulation by TLR-ligands (TLR-L) induces several genes that can regulate the immune response. In this study, we compared the ability of diverse TLR2-L to activate professional antigen presenting cells (pAPCs). We found that in comparison to whole non-replicating microorganism Mycobacterium butyricum, the smaller components; lipoteichoic acid and Pam3CSK4 significantly enhanced the expression of several pro-inflammatory mediators. These included IL-6, TNF-α and nitric oxide both at the mRNA and the protein levels. Moreover, the higher response was associated with a differential activation of nuclear transcription factor kappa-B (NF-κB) by the diverse TLR2-L. However, all three ligands enhanced antigen cross-presentation and T cell induction after virus infection to the same extent. In conclusion, the data highlight the potential for small components of TLR agonists to induce superior inflammatory immune responses than whole microbial preparation in the field of vaccine studies.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Vandana
authors.initials: V
authors.lastname: Gambhir
authors.forename: Christopher
authors.initials: C
authors.lastname: Yildiz
authors.forename: Rylend
authors.initials: R
authors.lastname: Mulder
authors.forename: Sarah
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Christina
authors.initials: C
authors.lastname: Guzzo
authors.forename: Myron
authors.initials: M
authors.lastname: Szewczuk
authors.forename: Katrina
authors.initials: K
authors.lastname: Gee
authors.forename: Sameh
authors.initials: S
authors.lastname: Basta
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000382:microbiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D055666:Lipopeptides / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D013682:Teichoic Acids / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015850:Interleukin-6; D055666:Lipopeptides; D008070:Lipopolysaccharides; D016328:NF-kappa B; C508075:Pam(3)CSK(4) peptide; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D009569:Nitric Oxide; C009900:lipoteichoic acid