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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

Praziquantel treatment does not alter SmLy6A and SmLy6B IgG1 age distribution profiles, but does decrease antigen-specific IgG1 reactivity.SmLy6A-, SmLy6B- and SmTAL1-specific IgG1 were measured before and 9 weeks after praziquantel treatment in a cohort of infected males (n = 216). A) Age–associated profiles of SmLy6A-, B) SmLy6B-, and C) SmTAL1-specific IgG1 responses pre- and post-praziquantel treatment. (D) Effect of praziquantel treatment on human IgG1 responses to SmLy6A, (E) SmLy6B and (F) SmTAL1. IgG1 levels for those individuals producing a detectable response (>mean+3xSD uninfected controls) to SmLy6A (n = 16), SmLy6B (n = 50) or SmTAL1 (n = 26) before treatment are shown and the median value is represented by a horizontal bar. P-values were calculated using a Wilcoxon signed-rank test comparing pre-treatment and post-treatment antibody levels.
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pntd.0003920.g005: Praziquantel treatment does not alter SmLy6A and SmLy6B IgG1 age distribution profiles, but does decrease antigen-specific IgG1 reactivity.SmLy6A-, SmLy6B- and SmTAL1-specific IgG1 were measured before and 9 weeks after praziquantel treatment in a cohort of infected males (n = 216). A) Age–associated profiles of SmLy6A-, B) SmLy6B-, and C) SmTAL1-specific IgG1 responses pre- and post-praziquantel treatment. (D) Effect of praziquantel treatment on human IgG1 responses to SmLy6A, (E) SmLy6B and (F) SmTAL1. IgG1 levels for those individuals producing a detectable response (>mean+3xSD uninfected controls) to SmLy6A (n = 16), SmLy6B (n = 50) or SmTAL1 (n = 26) before treatment are shown and the median value is represented by a horizontal bar. P-values were calculated using a Wilcoxon signed-rank test comparing pre-treatment and post-treatment antibody levels.

Mentions: To further analyse the endemic human antibody responses to rSmLy6A and rSmLy6B in this infected cohort, pre- and post-PZQ treatment antibody levels were measured. In addition to rSmLy6A and rSmLy6B, antibody levels against rSmTAL1 (a non-surface tegumental antigen previously known as Sm22.6), were compared to assess whether protein localization within the tegument may influence antibody responses. For IgG1 responses, anti-rSmLy6A and rSmLy6B showed no age-associated profile either pre- or post-PZQ treatment, with prevalence in all age groups comparable (Fig 5A and 5B). In contrast, SmTAL1-IgG1 responses showed clear age-associated profiles of increasing prevalence with age in both pre- and post-PZQ treatment (Fig 5C). This finding was also observed in the IgG4 and IgE responses where no age-associated relationships were observed pre- or post-PZQ treatment to SmLy6A and B, when compared to a positive association detected for rSmTAL1 (see S2 Table).


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)

Praziquantel treatment does not alter SmLy6A and SmLy6B IgG1 age distribution profiles, but does decrease antigen-specific IgG1 reactivity.SmLy6A-, SmLy6B- and SmTAL1-specific IgG1 were measured before and 9 weeks after praziquantel treatment in a cohort of infected males (n = 216). A) Age–associated profiles of SmLy6A-, B) SmLy6B-, and C) SmTAL1-specific IgG1 responses pre- and post-praziquantel treatment. (D) Effect of praziquantel treatment on human IgG1 responses to SmLy6A, (E) SmLy6B and (F) SmTAL1. IgG1 levels for those individuals producing a detectable response (>mean+3xSD uninfected controls) to SmLy6A (n = 16), SmLy6B (n = 50) or SmTAL1 (n = 26) before treatment are shown and the median value is represented by a horizontal bar. P-values were calculated using a Wilcoxon signed-rank test comparing pre-treatment and post-treatment antibody levels.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003920.g005: Praziquantel treatment does not alter SmLy6A and SmLy6B IgG1 age distribution profiles, but does decrease antigen-specific IgG1 reactivity.SmLy6A-, SmLy6B- and SmTAL1-specific IgG1 were measured before and 9 weeks after praziquantel treatment in a cohort of infected males (n = 216). A) Age–associated profiles of SmLy6A-, B) SmLy6B-, and C) SmTAL1-specific IgG1 responses pre- and post-praziquantel treatment. (D) Effect of praziquantel treatment on human IgG1 responses to SmLy6A, (E) SmLy6B and (F) SmTAL1. IgG1 levels for those individuals producing a detectable response (>mean+3xSD uninfected controls) to SmLy6A (n = 16), SmLy6B (n = 50) or SmTAL1 (n = 26) before treatment are shown and the median value is represented by a horizontal bar. P-values were calculated using a Wilcoxon signed-rank test comparing pre-treatment and post-treatment antibody levels.
Mentions: To further analyse the endemic human antibody responses to rSmLy6A and rSmLy6B in this infected cohort, pre- and post-PZQ treatment antibody levels were measured. In addition to rSmLy6A and rSmLy6B, antibody levels against rSmTAL1 (a non-surface tegumental antigen previously known as Sm22.6), were compared to assess whether protein localization within the tegument may influence antibody responses. For IgG1 responses, anti-rSmLy6A and rSmLy6B showed no age-associated profile either pre- or post-PZQ treatment, with prevalence in all age groups comparable (Fig 5A and 5B). In contrast, SmTAL1-IgG1 responses showed clear age-associated profiles of increasing prevalence with age in both pre- and post-PZQ treatment (Fig 5C). This finding was also observed in the IgG4 and IgE responses where no age-associated relationships were observed pre- or post-PZQ treatment to SmLy6A and B, when compared to a positive association detected for rSmTAL1 (see S2 Table).

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