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

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.

Relationship between Carotid Intima Media Thickness and Helminth Infections on Flores Island, Indonesia

“…However, the before mentioned have focused on the adaptive responses and include Tregs [6]–[9]. It should be noted that, in line with the current data, a recent study in Gabon found that S. haematobium infected children develop a more pro-inflammatory TLR-mediated response [30]. We did not observe substantial differences in STH species and their effects on CVD risk factors.…”

Differences in Innate Cytokine Responses between European and African Children

“…This is in contrast to studies where helminth infections were found to influence TLR responses or expression levels [18], [34], [38], [39]. This may be due to the difference between whole blood responses measured here and isolated peripheral blood mononuclear cells used in the other studies.…”

Not all parasites are protective

“…In contrast, T cells obtained from mice given DCs cotreated with SEA and Propionibacterium acnes antigen had a robust SEA-specific induction of IL-17 (34), supporting the view that helminth plus bacterial infections can drive significant pro-inflammatory events that are absent in helminth-only infected individuals. In accordance with this, peripheral blood mononuclear cells from Gabonese children infected with Schistosoma haematobium have enhanced TNFa output in response to Toll-like receptor (TLR)-2 agonists compared to cells from uninfected children [a similar trend was noted for challenge with the TLR4 agonist lipopolysaccharide (LPS)] (35). It has also been reported that DCs from individuals infected with N. americanus have increased expression of CD14, the LPS coreceptor and this would allow for the possibility of increased responsiveness to endotoxin (36).…”