Publications (5) View all
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Article: Schistosome infection is associated with enhanced whole blood IL-10 secretion in response to cercarial excretory/secretory products.
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ABSTRACT: Infection of the human host by schistosome parasites follows exposure of skin to free-swimming cercariae and is aided by the release of excretory/secretory (E/S) material which is rich in proteases and glycoconjugates. This material provides the initial stimulus to cells of the innate immune system. The study presented here is the first to examine human innate/early immune responsiveness to cercarial E/S in subjects from an area co-endemic for Schistosoma mansoni and S. haematobium. We report that in infected participants stimulation of whole blood cultures with cercarial E/S material (termed 0-3hRP) caused the early (within 24 hours) release of greater quantities of regulatory IL-10, compared to un-infected controls. Elevated levels of IL-10 but not pro-inflammatory TNFα or IL-8 were most evident in participants co-infected with S. mansoni and S. haematobium and was accompanied by a higher 0-3hRP-specific IL-10: TNFα ratio. We also report that glycosylated components within 0-3hRP appear to be important factors in the stimulation of IL-8, TNFα and IL-10 production by whole blood cells. © 2013 Blackwell Publishing Ltd.Parasite Immunology 02/2013; · 2.60 Impact Factor -
Article: Th17 cells are associated with pathology in human schistosomiasis.
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ABSTRACT: Background. Schistosome infections are often clinically silent, but some individuals develop severe pathological reactions. In several disease processes Th17 cells have been linked to tissue injuries, while regulatory T (Treg) cells are thought to down-modulate inflammatory reactions. We assessed whether bladder pathology in human Schistosoma haematobium infection is related to the balance of Th17 and Treg cells. Using a murine model of Schistosoma mansoni infection we further investigated whether the peripheral profiles reflected ongoing events in tissues.Methods. We characterized T helper subsets in the peripheral blood of children residing in a S. haematobium-endemic area and in peripheral blood as well as in spleen and hepatic granulomas of S. mansoni-infected high-pathology CBA and low-pathology C57BL/6 mice. S. haematobium-infected children with bladder pathology had a significantly higher percentage of Th17 cells than those without pathology. Moreover, the Th17/Treg ratios were significantly higher in children with pathology compared to infected children without pathology.Results. Percentages of IL-17-producing cells were significantly more abundant in the spleen and granulomas of CBA compared to C57BL/6 mice. This difference was also reflected in the peripheral blood.Conclusions. Our results indicate for the first time that Th17 cells may be involved in the pathogenesis of human schistosomiasis.The Journal of Infectious Diseases 10/2012; · 6.41 Impact Factor -
Article: Bladder Morbidity and Hepatic Fibrosis in Mixed Schistosoma haematobium and S. mansoni Infections: A Population-Wide Study in Northern Senegal.
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ABSTRACT: The global distribution map of schistosomiasis shows a large overlap of Schistosoma haematobium- and S. mansoni-endemic areas in Africa. Yet, little is known about the consequences of mixed Schistosoma infections for the human host. A recent study in two neighboring co-endemic communities in Senegal indicated that infection intensities of both species were higher in mixed than in single infections. Here, we investigated the relationship between mixed Schistosoma infections and morbidity in the same population. So far, this has only been studied in children. Schistosoma infection was assessed by microscopy. Schistosoma-specific morbidity was assessed by ultrasound according to WHO guidelines. Multivariable logistic regression models were used to identify independent risk factors for morbidity. Complete parasitological and morbidity data were obtained from 403 individuals. Schistosoma haematobium-specific bladder morbidity was observed in 83% and S. mansoni-specific hepatic fibrosis in 27% of the participants. Bladder morbidity was positively associated with S. haematobium infection intensity (OR = 1.9 (95% CI 1.3-2.9) for a 10-fold increase in intensity). Moreover, people with mixed infections tended to have less bladder morbidity than those with single S. haematobium infections (OR = 0.3 (95% CI 0.1-1.1)). This effect appeared to be related to ectopic S. mansoni egg elimination in urine. Hepatic fibrosis on the other hand was not related to S. mansoni infection intensity (OR = 0.9 (95% CI 0.6-1.3)), nor to mixed infections (OR = 1.0 (95% CI 0.7-1.7)). This is the first population-wide study on the relationship between mixed Schistosoma infections and morbidity. Mixed infections did not increase the risk of S. mansoni-associated morbidity. They even tended to reduce the risk of S. haematobium-associated morbidity, suggesting a protective effect of S. mansoni infection on bladder morbidity. These unexpected results may have important consequences for schistosomiasis control in co-endemic areas and warrant further investigation.PLoS Neglected Tropical Diseases 09/2012; 6(9):e1829. · 4.69 Impact Factor -
Article: Epidemiology of mixed Schistosoma mansoni and Schistosoma haematobium infections in northern Senegal.
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ABSTRACT: Due to the large overlap of Schistosoma mansoni- and Schistosoma haematobium-endemic regions in Africa, many people are at risk of co-infection, with potential adverse effects on schistosomiasis morbidity and control. Nonetheless, studies on the distribution and determinants of mixed Schistosoma infections have to date been rare. We conducted a cross-sectional survey in two communities in northern Senegal (n=857) to obtain further insight into the epidemiology of mixed infections and ectopic egg elimination. Overall prevalences of S. mansoni and S. haematobium infection were 61% and 50%, respectively, in these communities. Among infected subjects, 53% had mixed infections and 8% demonstrated ectopic egg elimination. Risk factors for mixed infection - i.e. gender, community of residence and age - were not different from what is generally seen in Schistosoma-endemic areas. Similar to overall S. mansoni and S. haematobium infections, age-related patterns of mixed infections showed the characteristic convex-shaped curve for schistosomiasis, with a rapid increase in children, a peak in adolescents and a decline in adults. Looking at the data in more detail however, the decline in overall S. haematobium infection prevalences and intensities appeared to be steeper than for S. mansoni, resulting in a decrease in mixed infections and a relative increase in single S. mansoni infections with age. Moreover, individuals with mixed infections had higher infection intensities of both S. mansoni and S. haematobium than those with single infections, especially those with ectopic egg elimination (P<0.05). High infection intensities in mixed infections, as well as age-related differences in infection patterns between S. mansoni and S. haematobium, may influence disease epidemiology and control considerably, and merit further studies into the underlying mechanisms of Schistosoma infections in co-endemic areas.International journal for parasitology 02/2012; 42(3):305-11. · 3.39 Impact Factor -
Article: Enhanced pro-inflammatory cytokine responses following Toll-like-receptor ligation in Schistosoma haematobium-infected schoolchildren from rural Gabon.
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ABSTRACT: 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. Peripheral 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. 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-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). 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.PLoS ONE 01/2011; 6(9):e24393. · 4.09 Impact Factor
