Maturation of dendritic cell 2 phenotype by a helminth glycan uses a Toll-like receptor 4-dependent mechanism.
The biology of pathogen-associated molecular patterns (PAMPs) stimulating APCs to differentiate into a Th1-promoting phenotype has been well characterized. Conversely, not a single pathogen product that promotes a Th2 phenotype has been rigorously identified. Strong Th2 responses and dendritic cell 2 maturation are driven by helminth extracts, and carbohydrates have been shown to be responsible for much of this activity. In this study, we show that a helminth carbohydrate, lacto-N-fucopentaose III (LNFPIII) functions as an innate Th2 promoter via its action on murine dendritic cells, with the alpha1-3-linked fucose required for this activity. In contrast to Th1-type PAMPs, which activate extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases, the Th2 PAMP LNFPIII preferentially activates extracellular signal-regulated kinase. Furthermore, the ability of LNFPIII to drive DC2 maturation is dependent on signaling via Toll-like receptor 4. These data support a new understanding of how APCs integrate signaling pathways to produce a Th1- or Th2-promoting phenotype.
Thomas
Paul G
PG
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Carter
Michele R
MR
Atochina
Olga
O
Da'Dara
Akram A
AA
Piskorska
Danuta
D
McGuire
Edward
E
Harn
Donald A
DA
D000595:Amino Acid Sequence; D000606:Amino Sugars / Q000276:immunology*; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002240:Carbohydrate Sequence; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D003911:Dextrans / Q000276:immunology; D005260:Female; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051193:Toll-Like Receptors
D000606:Amino Sugars; D000947:Antigens, Helminth; D003911:Dextrans; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C434666:lacto-N-fucopentaose III