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The Journal of Immunology, 2003, 171: 5837-5841.
Copyright © 2003 by The American Association of Immunologists

Maturation of Dendritic Cell 2 Phenotype by a Helminth Glycan Uses a Toll-Like Receptor 4-Dependent Mechanism 1

Paul G. Thomas2,*, Michele R. Carter2,*, Olga Atochina*, Akram A. Da’Dara*, Danuta Piskorska{dagger}, Edward McGuire{dagger} and Donald A. Harn3,*

* Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115; and {dagger} Neose Technologies, Horsham, PA 19044

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 {alpha}1–3-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.




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