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

Chalmers IW, Fitzsimmons CM, Brown M, Pierrot C, Jones FM, Wawrzyniak JM, Fernandez-Fuentes N, Tukahebwa EM, Dunne DW, Khalife J, Hoffmann KF - PLoS Negl Trop Dis (2015)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological, Environmental & Rural Sciences (IBERS), Aberystwyth University, Aberystwyth, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus

SmLy6 members demonstrate feature conservation characteristic of the uPAR/Ly6 superfamily.PSI-BLAST querying was used to identify eleven Ly6 family members in the S. mansoni genome (v 5.0). A) Diagrammatic representation of protein features characteristic of a single domain Ly6 protein. B) MUSCLE alignment of the deduced full-length amino acid sequences of SmLy6A—K sequences (SmLy6D sequence is split into SmLy6D 1st and 2nd domains). Predicted signal peptide sequences are highlighted in red. Conserved cysteines are shaded in yellow and labelled C1 to C10. Predicted GPI anchor sites are shaded in green and hydrophobic regions are highlighted in blue. The four amino acids shown to be essential in HsCD59 function [47] are indicated on the sequence by boxes. The amino acid numbering (indicated at left of alignment) begins at the initiating M of each protein.
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pntd.0003920.g001: SmLy6 members demonstrate feature conservation characteristic of the uPAR/Ly6 superfamily.PSI-BLAST querying was used to identify eleven Ly6 family members in the S. mansoni genome (v 5.0). A) Diagrammatic representation of protein features characteristic of a single domain Ly6 protein. B) MUSCLE alignment of the deduced full-length amino acid sequences of SmLy6A—K sequences (SmLy6D sequence is split into SmLy6D 1st and 2nd domains). Predicted signal peptide sequences are highlighted in red. Conserved cysteines are shaded in yellow and labelled C1 to C10. Predicted GPI anchor sites are shaded in green and hydrophobic regions are highlighted in blue. The four amino acids shown to be essential in HsCD59 function [47] are indicated on the sequence by boxes. The amino acid numbering (indicated at left of alignment) begins at the initiating M of each protein.

Mentions: Alignment of the amino acid sequences encoded by SmLy6A-K revealed low levels of identity (average 28%) across the putative uPAR/Ly6 domains, but did show conservation of the ten canonical cysteine residues across all SmLy6 proteins (Fig 1; HsCD59 sequence included as a representative Ly6 protein). A single uPAR/Ly6 domain was identified in all but one of the SmLy6 protein, with SmLy6D containing two. Examination of the two SmLy6D uPAR/Ly6 domains finds that the two cysteines (C7 and C8) which form the fifth disulphide bond in the uPAR/Ly6 domain are absent in the 1st domain but present in the second (Fig 1; yellow residues). For all eleven family members, the spacing between the C-terminal cysteines—C8 to C9 (0 or 1 residues) and C9 to C10 (3–5 residues)—is consistent with the inclusion of these proteins into the uPAR/Ly6 superfamily (Fig 1).


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

Chalmers IW, Fitzsimmons CM, Brown M, Pierrot C, Jones FM, Wawrzyniak JM, Fernandez-Fuentes N, Tukahebwa EM, Dunne DW, Khalife J, Hoffmann KF - PLoS Negl Trop Dis (2015)

SmLy6 members demonstrate feature conservation characteristic of the uPAR/Ly6 superfamily.PSI-BLAST querying was used to identify eleven Ly6 family members in the S. mansoni genome (v 5.0). A) Diagrammatic representation of protein features characteristic of a single domain Ly6 protein. B) MUSCLE alignment of the deduced full-length amino acid sequences of SmLy6A—K sequences (SmLy6D sequence is split into SmLy6D 1st and 2nd domains). Predicted signal peptide sequences are highlighted in red. Conserved cysteines are shaded in yellow and labelled C1 to C10. Predicted GPI anchor sites are shaded in green and hydrophobic regions are highlighted in blue. The four amino acids shown to be essential in HsCD59 function [47] are indicated on the sequence by boxes. The amino acid numbering (indicated at left of alignment) begins at the initiating M of each protein.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492491&req=5

pntd.0003920.g001: SmLy6 members demonstrate feature conservation characteristic of the uPAR/Ly6 superfamily.PSI-BLAST querying was used to identify eleven Ly6 family members in the S. mansoni genome (v 5.0). A) Diagrammatic representation of protein features characteristic of a single domain Ly6 protein. B) MUSCLE alignment of the deduced full-length amino acid sequences of SmLy6A—K sequences (SmLy6D sequence is split into SmLy6D 1st and 2nd domains). Predicted signal peptide sequences are highlighted in red. Conserved cysteines are shaded in yellow and labelled C1 to C10. Predicted GPI anchor sites are shaded in green and hydrophobic regions are highlighted in blue. The four amino acids shown to be essential in HsCD59 function [47] are indicated on the sequence by boxes. The amino acid numbering (indicated at left of alignment) begins at the initiating M of each protein.
Mentions: Alignment of the amino acid sequences encoded by SmLy6A-K revealed low levels of identity (average 28%) across the putative uPAR/Ly6 domains, but did show conservation of the ten canonical cysteine residues across all SmLy6 proteins (Fig 1; HsCD59 sequence included as a representative Ly6 protein). A single uPAR/Ly6 domain was identified in all but one of the SmLy6 protein, with SmLy6D containing two. Examination of the two SmLy6D uPAR/Ly6 domains finds that the two cysteines (C7 and C8) which form the fifth disulphide bond in the uPAR/Ly6 domain are absent in the 1st domain but present in the second (Fig 1; yellow residues). For all eleven family members, the spacing between the C-terminal cysteines—C8 to C9 (0 or 1 residues) and C9 to C10 (3–5 residues)—is consistent with the inclusion of these proteins into the uPAR/Ly6 superfamily (Fig 1).

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological, Environmental & Rural Sciences (IBERS), Aberystwyth University, Aberystwyth, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus