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Naturally-acquired cellular immune response against Plasmodium vivax merozoite surface protein-1 paralog antigen.

Changrob S, Leepiyasakulchai C, Tsuboi T, Cheng Y, Lim CS, Chootong P, Han ET - Malar. J. (2015)

Bottom Line: Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice.PvMSP1P-19 strongly induces a specific cellular immune response for protection against P. vivax compared with PvDBPII as the antigen induces activation of IFN-γ-producing effector cells following natural P. vivax exposure.Upon stimulation, PvMSP1P-19 has the potential to activate the recall response of Th1 effector memory cells that play a role in killing the parasite.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand. siriruk.ch@gmail.com.

ABSTRACT

Background: Plasmodium vivax merozoite surface protein-1 paralog (PvMSP1P) is a glycosylphosphatidylinositol-anchored protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection.

Methods: Peripheral blood mononuclear cells (PBMCs) from acute and recovery P. vivax infection were obtained for lymphocyte proliferation assay upon PvMSP1P-19 and PvDBP region II antigen stimulation. The culture supernatant was examined for the presence of the cytokines IL-2, TNF, IFN-γ and IL-10 by enzyme-linked immunosorbent assay (ELISA). To determine whether Th1 or Th2 have a memory response against PvMSP1P-19 and PvDBPII protein antigen, PBMCs from subjects who had recovered from P. vivax infection 8-10 weeks prior to the study were obtained for lymphocyte proliferation assay. Cytokine-producing cells were analysed by flow cytometry.

Results: IL-2 was detected at high levels in lymphocyte cultures from acutely infected P. vivax patients upon PvMSP1P-19 stimulation. Analysis of the Th1 or Th2 memory response in PBMC cultures from subjects who had recovered from P. vivax infection showed significantly elevated levels of PvMSP1P-19 and PvDBPII-specific IFN-γ-producing cells (P  <  0.05). Interestingly, the response of IFN-γ-producing cells in PvMSP1P stimulation was fourfold greater in recovered subjects than that in acute-infection patients. CD4(+) T cells were the major cell phenotype involved in the response to PvMSP1P-19 and PvDBPII antigen.

Conclusions: PvMSP1P-19 strongly induces a specific cellular immune response for protection against P. vivax compared with PvDBPII as the antigen induces activation of IFN-γ-producing effector cells following natural P. vivax exposure. Upon stimulation, PvMSP1P-19 has the potential to activate the recall response of Th1 effector memory cells that play a role in killing the parasite.

No MeSH data available.


Related in: MedlinePlus

T-cell responses to PvMSP1P-19 antigen using multiparameter flow cytometry. (a) Overall PvMSP1P-19-specific IL-2-producing cells. (b) IFN-γ-producing cells. Significance was determined by one-way ANOVA with Dunnett’s test. The level of significance was set at P  <  0.05.
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Fig4: T-cell responses to PvMSP1P-19 antigen using multiparameter flow cytometry. (a) Overall PvMSP1P-19-specific IL-2-producing cells. (b) IFN-γ-producing cells. Significance was determined by one-way ANOVA with Dunnett’s test. The level of significance was set at P  <  0.05.

Mentions: Many different IFN-γ-producing cell subsets, including to αβ T cells, γδ T cells and NK cells, have been shown to be capable of responding to Plasmodium parasites. Here, the phenotype of cells involved in the IFN-γ and IL-10 response upon PvMSP1P-19 stimulation was evaluated by flow cytometric analysis (Figure 3). Upon PvMSP1P-19 stimulation, CD4+ T cells were the major source of IL-2 and IFN-γ production. PvMSP1P-19 stimulation showed significantly higher IL-2 and IFN-γ levels than the medium control (IL-2, PvMSP1P-19  =  0.070%  ±  0.041%, unstimulated  =  0.041%  ±  0.023%, P  <  0.05; IFN-γ, PvMSP1P-19  =  0.112%  ±  0.053%, unstimulated  =  0.037%  ±  0.022%, P  <  0.05, Figures 4a-b). The effector CD4+ IFN-γ+ response to PvMSP1P-19 antigen was double that of CD8+ T cells (Figure 4a). Similarly, PvDBP region II antigen also had a high potential to induce CD4+ IFN+ T cell response (PvDBPII  =  0.094%  ±  0.046%, unstimulated  =  0.037%  ±  0.022%, P  <  0.05, Figure 4b). Phenotyping of IL-10-producing cells upon PvMSP1P-19 stimulation showed that CD4+ and CD8+ T cells were not major sources of IL-10 (CD4+, PvMSP1P-19  =  0.008%  ±  0.012%, unstimulated  =  0.002%  ±  0.002%, CD8+, PvMSP1P-19  =  0.008%  ±  0.009%, unstimulated  =  0.005%  ±  0.007%, P  >  0.05, Figure 5). These data suggest that CD4+ T cells dominate over CD8+ T cells in the responses against PvMSP1P-19 and PvDBP region II antigens.Figure 3


Naturally-acquired cellular immune response against Plasmodium vivax merozoite surface protein-1 paralog antigen.

Changrob S, Leepiyasakulchai C, Tsuboi T, Cheng Y, Lim CS, Chootong P, Han ET - Malar. J. (2015)

T-cell responses to PvMSP1P-19 antigen using multiparameter flow cytometry. (a) Overall PvMSP1P-19-specific IL-2-producing cells. (b) IFN-γ-producing cells. Significance was determined by one-way ANOVA with Dunnett’s test. The level of significance was set at P  <  0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4403936&req=5

Fig4: T-cell responses to PvMSP1P-19 antigen using multiparameter flow cytometry. (a) Overall PvMSP1P-19-specific IL-2-producing cells. (b) IFN-γ-producing cells. Significance was determined by one-way ANOVA with Dunnett’s test. The level of significance was set at P  <  0.05.
Mentions: Many different IFN-γ-producing cell subsets, including to αβ T cells, γδ T cells and NK cells, have been shown to be capable of responding to Plasmodium parasites. Here, the phenotype of cells involved in the IFN-γ and IL-10 response upon PvMSP1P-19 stimulation was evaluated by flow cytometric analysis (Figure 3). Upon PvMSP1P-19 stimulation, CD4+ T cells were the major source of IL-2 and IFN-γ production. PvMSP1P-19 stimulation showed significantly higher IL-2 and IFN-γ levels than the medium control (IL-2, PvMSP1P-19  =  0.070%  ±  0.041%, unstimulated  =  0.041%  ±  0.023%, P  <  0.05; IFN-γ, PvMSP1P-19  =  0.112%  ±  0.053%, unstimulated  =  0.037%  ±  0.022%, P  <  0.05, Figures 4a-b). The effector CD4+ IFN-γ+ response to PvMSP1P-19 antigen was double that of CD8+ T cells (Figure 4a). Similarly, PvDBP region II antigen also had a high potential to induce CD4+ IFN+ T cell response (PvDBPII  =  0.094%  ±  0.046%, unstimulated  =  0.037%  ±  0.022%, P  <  0.05, Figure 4b). Phenotyping of IL-10-producing cells upon PvMSP1P-19 stimulation showed that CD4+ and CD8+ T cells were not major sources of IL-10 (CD4+, PvMSP1P-19  =  0.008%  ±  0.012%, unstimulated  =  0.002%  ±  0.002%, CD8+, PvMSP1P-19  =  0.008%  ±  0.009%, unstimulated  =  0.005%  ±  0.007%, P  >  0.05, Figure 5). These data suggest that CD4+ T cells dominate over CD8+ T cells in the responses against PvMSP1P-19 and PvDBP region II antigens.Figure 3

Bottom Line: Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice.PvMSP1P-19 strongly induces a specific cellular immune response for protection against P. vivax compared with PvDBPII as the antigen induces activation of IFN-γ-producing effector cells following natural P. vivax exposure.Upon stimulation, PvMSP1P-19 has the potential to activate the recall response of Th1 effector memory cells that play a role in killing the parasite.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand. siriruk.ch@gmail.com.

ABSTRACT

Background: Plasmodium vivax merozoite surface protein-1 paralog (PvMSP1P) is a glycosylphosphatidylinositol-anchored protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection.

Methods: Peripheral blood mononuclear cells (PBMCs) from acute and recovery P. vivax infection were obtained for lymphocyte proliferation assay upon PvMSP1P-19 and PvDBP region II antigen stimulation. The culture supernatant was examined for the presence of the cytokines IL-2, TNF, IFN-γ and IL-10 by enzyme-linked immunosorbent assay (ELISA). To determine whether Th1 or Th2 have a memory response against PvMSP1P-19 and PvDBPII protein antigen, PBMCs from subjects who had recovered from P. vivax infection 8-10 weeks prior to the study were obtained for lymphocyte proliferation assay. Cytokine-producing cells were analysed by flow cytometry.

Results: IL-2 was detected at high levels in lymphocyte cultures from acutely infected P. vivax patients upon PvMSP1P-19 stimulation. Analysis of the Th1 or Th2 memory response in PBMC cultures from subjects who had recovered from P. vivax infection showed significantly elevated levels of PvMSP1P-19 and PvDBPII-specific IFN-γ-producing cells (P  <  0.05). Interestingly, the response of IFN-γ-producing cells in PvMSP1P stimulation was fourfold greater in recovered subjects than that in acute-infection patients. CD4(+) T cells were the major cell phenotype involved in the response to PvMSP1P-19 and PvDBPII antigen.

Conclusions: PvMSP1P-19 strongly induces a specific cellular immune response for protection against P. vivax compared with PvDBPII as the antigen induces activation of IFN-γ-producing effector cells following natural P. vivax exposure. Upon stimulation, PvMSP1P-19 has the potential to activate the recall response of Th1 effector memory cells that play a role in killing the parasite.

No MeSH data available.


Related in: MedlinePlus