Muropeptides trigger distinct activation profiles in macrophages and dendritic cells
| Autor: | Elena S. Fedenko, Boris V. Pinegin, Biana I. Alkhazova, Sergei F. Popilyuk, Khaitov Rakhim M, Mikhail Pashenkov, Vladimir V. Murugin, Vyacheslav L. L’vov |
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| Rok vydání: | 2010 |
| Předmět: |
Chemokine
medicine.medical_treatment Immunology Nod2 Signaling Adaptor Protein Peptidoglycan Biology Microbiology Immunomodulation chemistry.chemical_compound Th2 Cells In vivo Nod1 Signaling Adaptor Protein medicine Immunology and Allergy Macrophage Humans Antigen-presenting cell Th1-Th2 Balance Cells Cultured Pharmacology Innate immune system Macrophages Glycopeptides hemic and immune systems Cell Differentiation Dendritic cell Dendritic Cells Salmonella typhi Th1 Cells Cytokine chemistry biology.protein Cytokines |
| Zdroj: | International immunopharmacology. 10(8) |
| ISSN: | 1878-1705 |
| Popis: | Bacterial peptidoglycan and its muropeptide derivatives potently activate mammalian innate immune system and are promising immunomodulators and vaccine adjuvants. However, their effects on human antigen-presenting cells, such as dendritic cells (DCs) and Mphi, are not fully understood. Lysozyme treatment of PG from Salmonella typhi yielded three muropeptides, GlcNAc–MurNAc–L-Ala–D-isoGlu– meso -DAP (GM-3P), GlcNAc–MurNAc–L-Ala–D-isoGlu– meso -DAP–D-Ala (GM-4P), and a dimer (GM-4P) 2 , in which two GM-4P monomers are linked through their peptidic moieties. All three muropeptides induced TNF-α and IL-6 production by Mphi (GM-3P > GM-4P >> (GM-4P) 2 ), but failed to trigger TNF-α, IL-6 and IL-12p70 production by immature DCs. At the same time, muropeptide-stimulated DCs abundantly produced inflammatory chemokines IL-8, MIP-1α and MIP-1β, as well as displayed signs of phenotypic and functional maturation. Thus, muropeptide-dependent pro-inflammatory cytokine production is repressed in DCs. While this defect may be partly compensated in vivo by muropeptide-activated Mphi, neither Mphi nor DCs produce Th1- or Th17-polarizing cytokines upon muropeptide stimulation, which may contribute to the preferential induction of Th2 responses by muropeptides and should be taken into account when designing muropeptide-based immunomodulators and adjuvants. |
| Databáze: | OpenAIRE |
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