Enhanced pro-inflammatory cytokine responses following toll-like-receptor ligation in Schistosoma haematobium-infected schoolchildren from rural Gabon

L Meurs, L Labuda, AS Amoah, M Mbow, UA Ngoa, DA Boakye, S Mboup, TN Dièye, AP Mountford, JD Turner, PG Kremsner, K Polman, M Yazdanbakhsh, AA Adegnika

    Research output: Contribution to journalA1: Web of Science-article

    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. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zile 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-alpha and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants. PRINCIPAL FINDINGS: Infected 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-alpha responses than uninfected children and significantly higher TNF-alpha 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). CONCLUSIONS: 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 TLR ligation.
    Original languageEnglish
    JournalPLoS ONE
    Volume6
    Issue number9
    Pages (from-to)e24393
    Number of pages7
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Helminthic diseases
    • Schistosomiasis
    • Schistosoma haematobium
    • Schoolchildren
    • Immune response
    • Innate immunity
    • Cytokines
    • IL-10
    • Antigens
    • TNF
    • Inflammatory reactions
    • Rural
    • Gabon
    • Africa-Central

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