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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

16 Apr 2008

Marcia Triunfol

Source: PLoS Neglected Tropical Diseases (see original article)

Citation: Hartgers FC, Obeng BB, Kruize YCM, Duijvestein M, de Breij A, et al. (2008) 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. PLoS Negl Trop Dis 2(4): e227. doi:10.1371/journal.pntd.00002273

It has been almost 20 years since David P. Strachan (1) proposed the hygiene theory to explain the inverse relationship that exists between incidence of allergic diseases and exposure to pathogens. According to the theory, early exposure to microorganisms such as parasites, bacteria and virus reduces the incidence of allergies during life. The explanation is that early exposure to such organisms boosts the immune system to respond against infectious agents, whereas the lack of early exposure leads to an over-reactive immune system that strongly responds to harmless agents such as pollen and mite, among others.

Indeed, improvements in personal hygiene and sanitation conditions worldwide, especially in urban areas, have been followed by a significant decrease in parasitic infections, while the incidence of allergic and auto-immune diseases has increased. In areas where exposure to infectious agents is still high the incidence of allergies remains lower.

In this article, an international team of scientists that includes researchers in the United Kingdom, the Netherlands, and in the University of Ghana, found that lower expression of Toll-like receptors 2 (TLR2) is associated with both Schistosoma haematobium infection and with lower risk of allergy in children living in rural area in Ghana.

Toll-like receptors 2 have shown to play a role in allergic diseases. In studies not done in Africa, the expression levels of these receptors have shown to change following exposure to microorganisms.

Besides TLR2, the group has also investigated the role of the cytokine signalling molecules known as SOCS, which animal studies have shown to be involved in TLR signalling, and in immune responses to allergic disease – especially SOCS-3.

In this study, gene expression analysis was done to estimate mRNA levels of TLR2 and SOCS-3 in the whole blood, in 120 school children in a rural area in Ghana known to be highly endemic for helminth infections. Information on the child carrier status for S. haematobium was determined by the Katz-Katz method, which identifies the parasite’s eggs in stool samples. Skin reactivity to house dust mite was determined by the skin-prick test for mite allergen. Detection of total and mite-specific IgE was done with ELISA.

While 19% of schistosome negative children were positive for the mite skin test, only 11% of schistosome positive children had a mite skin test that was positive. As for TLR2 and SOCS-3 mRNA levels, children with positive skin reactivity to house dust mite had significantly higher expression of TLR2 and of SOCS-3. Conversely, the mRNA levels of TLR2 and SOCS-3 were lower in children infected with S. haematobium, but not in children infected with other types of hookworm infection. These findings suggest that the negative association between schistosome infection and the ability to modulate inflammatory reactions such as atopy may be a function of the low expression levels of TLR2 and SOCS-3, which in this case have the role of suppressing atopy.

This is the first study that shows an association between expression levels of TLR2 and atopy in non-European populations. All the previous studies were done with European populations.

If helminthes indeed present a protection against allergy and other inflammatory reactions, the introduction of vaccines in areas that are endemic for S. haematobium should be considered carefully, as helminth infection may drastically affect the vaccine efficacy. On the other hand, a better understanding of these molecular pathways may provide new strategies for controlling inflammatory diseases other than allergies.

References

1. Strachan DP (1989). Hay fever, hygiene, and household size. British Medical Journal 299: 1259-1260.

For more information on the immunological reaction that helminthes trigger in humans, see:

Díaz A and Allen JE (2007). Mapping immune response profiles: the emerging scenario from helminth immunology. Eur J Immunol 37(12), 3319-26.

© 2008 Hartgers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Source

Title:
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.

Authors:
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

References:
PLoS Negl Trop Dis 2008: Vol. 2 no. 4, pp. e227

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.

PMID: 18414649
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