Characterization of Parelaphostrongylus tenuis excretory glands and identification of alpha-Gal-modified excreted/secreted proteins

Abstract

Adult Parelaphostrongylus tenuis induce a concomitant immunity that protects their deer host against subsequent infections. Although this phenomenon is common among longlived parasitic helminths, molecular mechanisms that mediate concomitant immunity remain unknown. Alpha-Gal is a disaccharide that is stage-restricted, synthesized exclusively by adult stage P. tenuis, suggesting a potential role in mediating concomitant immunity. Current studies identified excretory glands as the principle source of alpha-Gal-modified glycoproteins. Secretory granules are the dominant component of these specialized cells, confirming a primary role for excretory glands in protein secretion and, by extension, parasitism. The alpha-Gal epitope is also synthesized within the deer host and so parasite-derived alpha-Gal is poised to promote immune modulation. A model is proposed for alpha-Gal-mediated modulation of host immune responses to promote concomitant immunity. Two-dimensional immunoblots and mass spectrometry identified galectin and/or Ancylostoma-secreted protein homologues as likely candidates for modification by alpha-Gal.