Requirement for core 2 O-glycans for optimal resistance to helminth infection

PLoS One. 2013;8(3):e60124. doi: 10.1371/journal.pone.0060124. Epub 2013 Mar 29.

Abstract

The migration of lymphocytes to the small intestine is controlled by expression of the integrin α4β7 and the chemokine receptor CCR9. However, the molecules that specifically regulate migration to the large intestine remain unclear. Immunity to infection with the large intestinal helminth parasite Trichuris muris is dependent upon CD4(+) T cells that migrate to the large intestine. We examine the role of specific chemokine receptors, adhesion molecules and glycosyltransferases in the development of protective immunity to Trichuris. Mice deficient in expression of the chemokine receptors CCR2 or CCR6 were resistant to infection with Trichuris. Similarly, loss of CD34, CD43, CD44 or PSGL-1 had no effect on resistance to infection. In contrast, simultaneous deletion of the Core2 β1,6-N-acetylglucosaminyltransferase (C2GnT) enzymes C2GnT1 and C2Gnt2 resulted in delayed expulsion of worms. These results suggest that C2GnT-dependent modifications may play a role in migration of protective immune cells to the large intestine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Intestine, Large / metabolism*
  • Intestine, Large / parasitology*
  • Leukosialin / genetics
  • Leukosialin / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism
  • Polysaccharides / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / metabolism
  • Trichuriasis / genetics
  • Trichuriasis / metabolism*
  • Trichuris / pathogenicity*

Substances

  • Antigens, CD34
  • Hyaluronan Receptors
  • Leukosialin
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Polysaccharides
  • Receptors, CCR2
  • Receptors, CCR6
  • N-Acetylglucosaminyltransferases
  • beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3