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Muropeptides trigger distinct activation profiles in macrophages and dendritic cells.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2010 Aug; Vol. 10 (8), pp. 875-82. Date of Electronic Publication: 2010 May 10. - Publication Year :
- 2010
-
Abstract
- 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-alpha and IL-6 production by Mphi (GM-3P>GM-4P>>(GM-4P)(2)), but failed to trigger TNF-alpha, IL-6 and IL-12p70 production by immature DCs. At the same time, muropeptide-stimulated DCs abundantly produced inflammatory chemokines IL-8, MIP-1 alpha and MIP-1 beta, 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.<br /> ((c) 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Cell Differentiation drug effects
Cell Differentiation immunology
Cells, Cultured
Cytokines biosynthesis
Cytokines genetics
Cytokines metabolism
Dendritic Cells immunology
Dendritic Cells metabolism
Dendritic Cells pathology
Glycopeptides chemistry
Glycopeptides isolation & purification
Glycopeptides pharmacology
Humans
Immunomodulation
Macrophages immunology
Macrophages metabolism
Macrophages pathology
Nod1 Signaling Adaptor Protein genetics
Nod1 Signaling Adaptor Protein immunology
Nod1 Signaling Adaptor Protein metabolism
Nod2 Signaling Adaptor Protein genetics
Nod2 Signaling Adaptor Protein immunology
Nod2 Signaling Adaptor Protein metabolism
Peptidoglycan chemistry
Peptidoglycan isolation & purification
Th1 Cells immunology
Th1-Th2 Balance
Th2 Cells immunology
Dendritic Cells drug effects
Macrophages drug effects
Peptidoglycan pharmacology
Salmonella typhi
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 20438865
- Full Text :
- https://doi.org/10.1016/j.intimp.2010.04.025