Enhanced Pro-Inflammatory Cytokine Responses following Toll-Like-Receptor Ligation in Schistosoma haematobium-Infected Schoolchildren from Rural Gabon

Maria Yazdanbakhsh,Lynn Meurs,Ayola Akim Adegnika,Katja Polman,Tandakha Ndiaye Dièye,Souleymane Mboup,Lucja Labuda,Peter Gottfried Kremsner,Daniel Adjei Boakye,Joseph D Turner,Adrian P Mountford,Ulysse Ateba Ngoa,Moustapha Mbow,Abena Serwaa Amoah

doi:10.1371/journal.pone.0024393

Abstract

Background Schistosoma infection is thought to lead to down-regulation of the host's immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands.MethodologyPeripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zilé in Gabon. PBMCs were incubated for 24 h and 72 h with various TLR ligands, as well as schistosomal egg antigen (SEA) and adult worm antigen (AWA). Pro-inflammatory TNF-α and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants.Principal FindingsInfected children produced higher adaptive IL-10 responses than uninfected children against schistosomal antigens (72 h incubation). On the other hand, infected children had higher TNF-α responses than uninfected children and significantly higher TNF-α to IL-10 ratios in response to FSL-1 and Pam3, ligands of TLR2/6 and TLR2/1 respectively. A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation).ConclusionsThis pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response. This suggests that S. haematobium infection does not suppress the host's innate immune system in the context of single TLR ligation.

Highlights

Schistosomiasis is a parasitic disease of major public health importance and is largely chronic in nature
A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation). This pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response
This suggests that S. haematobium infection does not suppress the host’s innate immune system in the context of single Toll-like receptor (TLR) ligation

Summary

Introduction

Schistosomiasis is a parasitic disease of major public health importance and is largely chronic in nature. Effects of schistosomal infection on adaptive immunity are widely studied in this context and it has been shown that chronic schistosomiasis inhibits in vitro proliferation of human lymphocytes in response to schistosomal antigens [8,9]. Similar mechanisms might explain the impaired reaction to tetanus toxoid observed in Schistosoma mansoni-infected individuals [18]. Another feature of IL-10 is that it might suppress atopy in Schistosoma haematobium-infected children [15,19]. Schistosoma infection is thought to lead to down-regulation of the host’s immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands

Methods

Results

Conclusion