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Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3.

Guiyedi V, Bécavin C, Herbert F, Gray J, Cazenave PA, Kombila M, Crisanti A, Fesel C, Pied S - Malar. J. (2015)

Bottom Line: In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children.IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM.Altogether, these results indicate that a self-reactive polyclonal response associated with increased IgG to MSP3 and high plasma levels of IL-10 and IFN-γ may contribute to protective immune mechanisms triggered in asymptomatic P. falciparum infection in Gabonese children.

View Article: PubMed Central - PubMed

Affiliation: CIIL-Centre for Infection and Immunity of Lille, INSERM U1019 - CNRS UMR 8204, Lille University, Institut Pasteur de Lille, 1, rue du Professeur Calmette, Cedex 59019, Lille, France. guidyvin@hotmail.com.

ABSTRACT

Background: Mechanisms of acquired protection to malaria in asymptomatic Plasmodium falciparum carriers are only partially understood. Among them, the role plays by the self-reactive antibodies has not been clarified yet. In this study, the relationship between repertoires of circulating self-reactive and parasite-specific immunoglobulin G (IgG), their correlation with cytokine levels, and their association with protection against malaria was investigated in asymptomatic Plasmodium falciparum-infected Gabonese children.

Methods: The diversity of P. falciparum-specific antibody repertoire was analysed using a protein micro-array immunoassay, the total auto-antibody repertoire by quantitative immunoblotting and circulating cytokine levels were measured by ELISA in endemic controls (EC) and P. falciparum-infected children from Gabon with asymptomatic (AM) or mild malaria (MM). The association of self- and parasite-specific antibody repertoires with circulating cytokines was evaluated using single linkage hierarchical clustering, Kruskal-Wallis tests and Spearman's rank correlation.

Results: Children with AM exhibited an IgG response to merozoite surface protein 3 (MSP3) but not to MSP1-19, although their levels of total P. falciparum-specific IgG were similar to those in the MM group. Moreover, the asymptomatic children had increased levels of autoantibodies recognising brain antigens. In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children. These two groups also exhibited significant correlations between plasma levels of IL-10 and IFN-γ with age and with total plasma IgG levels. IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM.

Conclusions: Altogether, these results indicate that a self-reactive polyclonal response associated with increased IgG to MSP3 and high plasma levels of IL-10 and IFN-γ may contribute to protective immune mechanisms triggered in asymptomatic P. falciparum infection in Gabonese children.

No MeSH data available.


Related in: MedlinePlus

Cytokines levels in respect to clinical status. Plasma levels of IFN-γ (A) TNF (B) and IL-10 (C) in the EC, AM and MM groups at the day of hospitalization and before treatment.
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Fig5: Cytokines levels in respect to clinical status. Plasma levels of IFN-γ (A) TNF (B) and IL-10 (C) in the EC, AM and MM groups at the day of hospitalization and before treatment.

Mentions: Levels in plasma of IFN-γ, TNF and IL-10 were assessed in all children. Plasma concentrations of IFN-g-γ were similar in the three groups (Figure 5A), whereas TNF levels were significantly lower in MM than EC or AM (p = 0.001 and 0.01, respectively) (Figure 5B). In contrast, IL-10 levels were significantly increased during infection in AM and MM groups (p = 0.03 and p < 0.001, respectively; Figure 5C). IL-10 concentrations was significantly correlated with parasite load on day 0 in infected children (R-Spearman = +0.71; p < 0.001) (Figure 5D) and decreased significantly at day 7 in MM patients after treatment with anti-malarial drugs (p = 0.007, paired t-test), when no parasites were detectable in peripheral blood (see Additional file 5). However, there was no correlation between cytokine responses and age.Figure 5


Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3.

Guiyedi V, Bécavin C, Herbert F, Gray J, Cazenave PA, Kombila M, Crisanti A, Fesel C, Pied S - Malar. J. (2015)

Cytokines levels in respect to clinical status. Plasma levels of IFN-γ (A) TNF (B) and IL-10 (C) in the EC, AM and MM groups at the day of hospitalization and before treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4419484&req=5

Fig5: Cytokines levels in respect to clinical status. Plasma levels of IFN-γ (A) TNF (B) and IL-10 (C) in the EC, AM and MM groups at the day of hospitalization and before treatment.
Mentions: Levels in plasma of IFN-γ, TNF and IL-10 were assessed in all children. Plasma concentrations of IFN-g-γ were similar in the three groups (Figure 5A), whereas TNF levels were significantly lower in MM than EC or AM (p = 0.001 and 0.01, respectively) (Figure 5B). In contrast, IL-10 levels were significantly increased during infection in AM and MM groups (p = 0.03 and p < 0.001, respectively; Figure 5C). IL-10 concentrations was significantly correlated with parasite load on day 0 in infected children (R-Spearman = +0.71; p < 0.001) (Figure 5D) and decreased significantly at day 7 in MM patients after treatment with anti-malarial drugs (p = 0.007, paired t-test), when no parasites were detectable in peripheral blood (see Additional file 5). However, there was no correlation between cytokine responses and age.Figure 5

Bottom Line: In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children.IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM.Altogether, these results indicate that a self-reactive polyclonal response associated with increased IgG to MSP3 and high plasma levels of IL-10 and IFN-γ may contribute to protective immune mechanisms triggered in asymptomatic P. falciparum infection in Gabonese children.

View Article: PubMed Central - PubMed

Affiliation: CIIL-Centre for Infection and Immunity of Lille, INSERM U1019 - CNRS UMR 8204, Lille University, Institut Pasteur de Lille, 1, rue du Professeur Calmette, Cedex 59019, Lille, France. guidyvin@hotmail.com.

ABSTRACT

Background: Mechanisms of acquired protection to malaria in asymptomatic Plasmodium falciparum carriers are only partially understood. Among them, the role plays by the self-reactive antibodies has not been clarified yet. In this study, the relationship between repertoires of circulating self-reactive and parasite-specific immunoglobulin G (IgG), their correlation with cytokine levels, and their association with protection against malaria was investigated in asymptomatic Plasmodium falciparum-infected Gabonese children.

Methods: The diversity of P. falciparum-specific antibody repertoire was analysed using a protein micro-array immunoassay, the total auto-antibody repertoire by quantitative immunoblotting and circulating cytokine levels were measured by ELISA in endemic controls (EC) and P. falciparum-infected children from Gabon with asymptomatic (AM) or mild malaria (MM). The association of self- and parasite-specific antibody repertoires with circulating cytokines was evaluated using single linkage hierarchical clustering, Kruskal-Wallis tests and Spearman's rank correlation.

Results: Children with AM exhibited an IgG response to merozoite surface protein 3 (MSP3) but not to MSP1-19, although their levels of total P. falciparum-specific IgG were similar to those in the MM group. Moreover, the asymptomatic children had increased levels of autoantibodies recognising brain antigens. In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children. These two groups also exhibited significant correlations between plasma levels of IL-10 and IFN-γ with age and with total plasma IgG levels. IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM.

Conclusions: Altogether, these results indicate that a self-reactive polyclonal response associated with increased IgG to MSP3 and high plasma levels of IL-10 and IFN-γ may contribute to protective immune mechanisms triggered in asymptomatic P. falciparum infection in Gabonese children.

No MeSH data available.


Related in: MedlinePlus