title: Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum.
abstract: Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted N-glycans with terminal mannose residues, Galβ1-4GlcNAc (LacNAc) and Galβ1-4(Fucα1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAcβ1-4(GlcNAcβ1)n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAcβ1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage- and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection.
authors.affiliation: Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Smit
authors.affiliation: Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Christiaan L
authors.initials: CL
authors.lastname: Kies
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: Hamish E G
authors.initials: HE
authors.lastname: McWilliam
authors.affiliation: Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Els N T
authors.initials: EN
authors.lastname: Meeusen
authors.affiliation: Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
authors.affiliation: Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands A.van_Diepen@lumc.nl.
authors.forename: Angela
authors.initials: A
authors.lastname: van Diepen
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000921:Antibody-Producing Cells / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology*; D005260:Female; D006028:Glycosphingolipids / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D011134:Polysaccharides / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000469:parasitology
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D006028:Glycosphingolipids; D011134:Polysaccharides