Modulation of host immune responses by helminth glycans

Immunol Rev. 2009 Jul;230(1):247-57. doi: 10.1111/j.1600-065X.2009.00799.x.

Abstract

Parasitic infections regulate/alter host immune responses. Among parasitic infections, helminth infection often leads to systemic immune suppression or anergy. Helminth infection or helminth extracts drive CD4+ T-helper (Th) cell responses towards Th2 type and activate antigen-presenting cells (APCs) such that these cells express an anti-inflammatory phenotype. Among the myriad molecules present on or secreted by helminth parasites, glycans have been shown to be key in inducing Th2-type and anti-inflammatory immune responses. The majority of studies on immune modulatory helminth glycans have focused on Lacto-N-fucopentaose III and LewisX. When presented as glycol-conjugates, with multiple copies of the sugars conjugated to a carrier molecule, these compounds activate APCs, inducing an alternative activation pattern, whose phenotypic profile is substantially different than that seen using pro-inflammatory activators such as lipopolysaccharide. Though the mechanism of APC activation by LNFPIII/LewisX glycoconjugates has not been fully elucidated, it involves C-type lectin ligation on the surface of APCs, with subsequent antagonism of Toll-like receptor signaling. In this article, we discuss the APC surface receptors known to play roles in LNFPIII/LewisX induced alternative activation of APCs. We also discuss what is currently known regarding downstream signaling pathways, closing with a discussion of future research directions for this field of investigation including the potential use of immune modulatory glycans as vaccine adjuvants and anti-inflammatory therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Sugars / immunology
  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / parasitology
  • Antigens, Helminth / immunology*
  • Helminths / immunology*
  • Humans
  • Lewis X Antigen / immunology
  • Mice
  • Polysaccharides / immunology*
  • Signal Transduction / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Th2 Cells / parasitology
  • Toll-Like Receptor 4 / immunology

Substances

  • Amino Sugars
  • Antigens, Helminth
  • Lewis X Antigen
  • Polysaccharides
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • lacto-N-fucopentaose III