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Lower expression of TLR2 and SOCS-3 is associated with Schistosoma haematobium infection and with lower risk for allergic reactivity in children living in a rural area in Ghana.

Hartgers FC, Obeng BB, Kruize YC, Duijvestein M, de Breij A, Amoah A, Larbi IA, van Ree R, Wilson MD, Rodrigues LC, Boakye DA, Yazdanbakhsh M - PLoS Negl Trop Dis (2008)

Bottom Line: The mRNA expression of several genes of the innate immune system that have been associated with microbial exposure and allergy was examined in 120 school children in a rural area in Ghana.The analysis of gene expression in ex vivo whole blood samples reflected the levels of corresponding proteins.Using this approach in a population of school children in whom the presence of Schistosoma haematobium infection was associated with protection from atopic reactivity, we found that the level of TLR2 and SOCS-3, genes associated with atopy in the children, were significantly downregulated by presence of S. haematobium infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Leiden University Medical Centre, Leiden, The Netherlands. F.C.Hartgers@lumc.nl

ABSTRACT

Background: Helminth infections are prevalent in rural areas of developing countries and have in some studies been negatively associated with allergic disorders and atopy. In this context little is known of the molecular mechanisms of modulation involved. We have characterized the innate immune responses, at the molecular level, in children according to their helminth infection status and their atopic reactivity to allergens.

Methodology/principal findings: The mRNA expression of several genes of the innate immune system that have been associated with microbial exposure and allergy was examined in 120 school children in a rural area in Ghana. Helminth infections were common and atopy rare in the study area. The analysis of gene expression in ex vivo whole blood samples reflected the levels of corresponding proteins. Using this approach in a population of school children in whom the presence of Schistosoma haematobium infection was associated with protection from atopic reactivity, we found that the level of TLR2 and SOCS-3, genes associated with atopy in the children, were significantly downregulated by presence of S. haematobium infection.

Conclusions: S. haematobium infections modulate the expression of genes of the innate immune system (TLR2 and SOCS-3); these are genes that are associated with increased allergic inflammatory processes, providing a molecular link between the negative association of this infection and atopy in rural children in Ghana.

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Related in: MedlinePlus

Expression of TLR2 and SOCS-3 mRNA in cell subsets.Mean of relative mRNA expression of TLR2 (A) and SOCS-3 (B) in T cells (CD3), monocytes (CD14) and cells depleted of T cells and monocytes (rest) from 5 donors. Y error bars indicate the standard error of the mean from each group. (C) Mean expression levels of TLR2 and SOCS-3 in T cells, monocytes and the rest of the cells corrected for the percentages of cells within the PBMC population for each donor.
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pntd-0000227-g003: Expression of TLR2 and SOCS-3 mRNA in cell subsets.Mean of relative mRNA expression of TLR2 (A) and SOCS-3 (B) in T cells (CD3), monocytes (CD14) and cells depleted of T cells and monocytes (rest) from 5 donors. Y error bars indicate the standard error of the mean from each group. (C) Mean expression levels of TLR2 and SOCS-3 in T cells, monocytes and the rest of the cells corrected for the percentages of cells within the PBMC population for each donor.

Mentions: To determine the source of TLR2 and SOCS-3 expression in whole blood samples, monocytes and T cells were isolated from five donors. Although the mRNA expression of TLR2 was high in monocytes (63 to 275-fold higher than in T cells, Figure 3A), correction for the percentages of monocytes and T cells in the peripheral blood mononuclear cells, indicated that monocytes, T cells and other cells contributed similarly to the TLR2 expression measured in whole blood (Figure 3C). In contrast, the mRNA expression of SOCS-3 could clearly be attributed to the T cell fraction with little contribution from monocytes or other cells (Figure 3B–C).


Lower expression of TLR2 and SOCS-3 is associated with Schistosoma haematobium infection and with lower risk for allergic reactivity in children living in a rural area in Ghana.

Hartgers FC, Obeng BB, Kruize YC, Duijvestein M, de Breij A, Amoah A, Larbi IA, van Ree R, Wilson MD, Rodrigues LC, Boakye DA, Yazdanbakhsh M - PLoS Negl Trop Dis (2008)

Expression of TLR2 and SOCS-3 mRNA in cell subsets.Mean of relative mRNA expression of TLR2 (A) and SOCS-3 (B) in T cells (CD3), monocytes (CD14) and cells depleted of T cells and monocytes (rest) from 5 donors. Y error bars indicate the standard error of the mean from each group. (C) Mean expression levels of TLR2 and SOCS-3 in T cells, monocytes and the rest of the cells corrected for the percentages of cells within the PBMC population for each donor.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2291570&req=5

pntd-0000227-g003: Expression of TLR2 and SOCS-3 mRNA in cell subsets.Mean of relative mRNA expression of TLR2 (A) and SOCS-3 (B) in T cells (CD3), monocytes (CD14) and cells depleted of T cells and monocytes (rest) from 5 donors. Y error bars indicate the standard error of the mean from each group. (C) Mean expression levels of TLR2 and SOCS-3 in T cells, monocytes and the rest of the cells corrected for the percentages of cells within the PBMC population for each donor.
Mentions: To determine the source of TLR2 and SOCS-3 expression in whole blood samples, monocytes and T cells were isolated from five donors. Although the mRNA expression of TLR2 was high in monocytes (63 to 275-fold higher than in T cells, Figure 3A), correction for the percentages of monocytes and T cells in the peripheral blood mononuclear cells, indicated that monocytes, T cells and other cells contributed similarly to the TLR2 expression measured in whole blood (Figure 3C). In contrast, the mRNA expression of SOCS-3 could clearly be attributed to the T cell fraction with little contribution from monocytes or other cells (Figure 3B–C).

Bottom Line: The mRNA expression of several genes of the innate immune system that have been associated with microbial exposure and allergy was examined in 120 school children in a rural area in Ghana.The analysis of gene expression in ex vivo whole blood samples reflected the levels of corresponding proteins.Using this approach in a population of school children in whom the presence of Schistosoma haematobium infection was associated with protection from atopic reactivity, we found that the level of TLR2 and SOCS-3, genes associated with atopy in the children, were significantly downregulated by presence of S. haematobium infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Leiden University Medical Centre, Leiden, The Netherlands. F.C.Hartgers@lumc.nl

ABSTRACT

Background: Helminth infections are prevalent in rural areas of developing countries and have in some studies been negatively associated with allergic disorders and atopy. In this context little is known of the molecular mechanisms of modulation involved. We have characterized the innate immune responses, at the molecular level, in children according to their helminth infection status and their atopic reactivity to allergens.

Methodology/principal findings: The mRNA expression of several genes of the innate immune system that have been associated with microbial exposure and allergy was examined in 120 school children in a rural area in Ghana. Helminth infections were common and atopy rare in the study area. The analysis of gene expression in ex vivo whole blood samples reflected the levels of corresponding proteins. Using this approach in a population of school children in whom the presence of Schistosoma haematobium infection was associated with protection from atopic reactivity, we found that the level of TLR2 and SOCS-3, genes associated with atopy in the children, were significantly downregulated by presence of S. haematobium infection.

Conclusions: S. haematobium infections modulate the expression of genes of the innate immune system (TLR2 and SOCS-3); these are genes that are associated with increased allergic inflammatory processes, providing a molecular link between the negative association of this infection and atopy in rural children in Ghana.

Show MeSH
Related in: MedlinePlus