Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment

Iain W Chalmers, Colin M Fitzsimmons, Martha Brown, Christine Pierrot, Frances M. Jones, Jakub M Wawrzyniak, Narcis Fernandez-Fuentes, Edridah M. Tukahebwa, David W Dunne, Jamal Khalife, Karl F Hoffmann

Research output: Contribution to journalArticlepeer-review

13 Citations (SciVal)
183 Downloads (Pure)

Abstract

Background
The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored.

Methodology/Principal Findings
Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1.

Conclusions/Significance
Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities.

Author Summary
Adult schistosome parasites can live in the human bloodstream for years without being adversely affected by the host immune response. Identifying which proteins are on the surface of the parasite and understanding how they contribute to long-term host/parasite relationships is an essential step in developing novel intervention strategies. Here, utilising a comprehensive bioinformatics approach to identify Schistosoma mansoni gene products sharing distinct surface-associated features including signal peptides, hydrophobic C-termini, disulfide bonds and uPAR/Ly6 domains, we identified eleven proteins of interest. These proteins, reassuringly, include three representatives previously found associated with the schistosome surface (here termed SmLy6A, SmLy6B and SmLy6D) as well as three novel members (SmLy6G, SmLy6H and SmLy6J). To identify if surface-associated SmLy6 members are recognized by S. mansoni infected individuals, we specifically examined antibody responses to SmLy6A and SmLy6B in an endemic human population. Our work expands the number of putative cell surface associated schistosome proteins and provides a greater understanding of the dynamics of antibody responses in endemic communities against two representatives.
Original languageEnglish
Article numbere0003920
Pages (from-to)e0003920
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 2015

Keywords

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Animals
  • Antibodies, Helminth/blood
  • Antigens, Helminth/chemistry
  • Child
  • Cohort Studies
  • Humans
  • Immunoglobulin G/blood
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Multigene Family
  • Praziquantel/administration & dosage
  • Rats, Inbred F344
  • Schistosoma mansoni/chemistry
  • Schistosomiasis mansoni/blood
  • Sequence Alignment
  • Young Adult

Fingerprint

Dive into the research topics of 'Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment'. Together they form a unique fingerprint.

Cite this