Association of IL-9, IL-10, and IL-17 Cytokines With Hepatic Fibrosis in Human Schistosoma mansoni Infection
Karine Garcez Schuster FrancoFábio Jorge Ramalho de AmorimMário Adriano SantosCarla Virgínia Vieira RollembergFabrícia Alvisi de OliveiraAlex Vianey Callado FrançaCamilla Natália Oliveira SantosLucas Sousa MagalhãesRodrigo Anselmo CazzanigaFrederico Santana de LimaLuciana BenevidesVanessa CarregaroJoão S. SilvaHugo Leite de Farias BritoDaniel Alvarenga FernandesÂngela Maria da SilvaRoque Pacheco de AlmeidaMárcio Bezerra‐SantosAmélia Ribeiro de Jesus
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Abstract:
This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP—10 μg/ml) or egg (SEA—10 μg/ml) antigens or purified protein derivative of turberculin (PPD—10 μg/ml) or phytohemagglutinin (PHA—1 μg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17 , IL10 , and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.Keywords:
Schistosoma
Hepatic fibrosis
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"Failure of Plasma from Human Schistosomiasis Mansoni Patients to Protect Mice from Schistosoma Mansoni Cercarial Challenge" published on Jul 1977 by The American Society of Tropical Medicine and Hygiene.
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Tropical disease
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"Comparative Study of Schistosoma Mansoni Isolated from Patients with Hepatosplenic and Intestinal Clinical Forms of Schistosomiasis" published on Sep 1984 by The American Society of Tropical Medicine and Hygiene.
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A number of Erythrocebus patas monkeys have been experimentally infected only once, with Schistosoma mansoni local strain. The various parasitological, biological and immunological observations show that E. patas is a very adequate host to Schistosoma mansoni and that it develops an intestinal schistosomiasis parasitologically very close to human schistosomiasis. It is noted that in this case of single infection E. patas reactions are the same as the other species generally used in the experiments on S. mansoni.
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Immunoadjuvant
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In some regions of the world, co-existence of schistosomiasis and hepatitis C (HCV) infection is common. Because the morbidity in human schistosomiasis is primarily due to host cell-mediated immune response, it was of interest to determine the effects on Schistosoma mansoni infection of an immune stimulator used in the standard treatment of HCV infection. Schistosoma mansoni-infected mice were treated with PEG-interferon-α-2a (PEG-IFN-α) by subcutaneous injection. Groups 1, 2, and 3 received 0.2 µg, 0.6 µg, and 1 µg PEG-IFN-α/wk, respectively, while group 4 received saline. The total worm burden was lower in all treated groups, with a maximal reduction of 35% after 9 wk of treatment with 1 µg PEG-IFN-α. Interferon treatment also increased the proportion of single worms over pairs. Ova counts in intestine and liver, as well as the number of liver granulomas, were greatly decreased at all time points for all treated groups. PEG-IFN-α also had inhibitory effects on the size of granulomas after 4 wk of treatment. The results suggest that PEG-IFN-α may be worth investigating for the treatment of human schistosomiasis when standard oral agents cannot be used, or when rapid inhibition of granuloma formation may be a priority.
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A case of cutaneous schistosomiasis with lesions on the trunk caused by eggs of Schistosoma mansoni is described. A brief review of the reported cases of cutaneous ectopic schistosomiasis by S. mansoni in made. The different forms of cutaneous lesions caused by schistosoma are considered.
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C57BL/6 mice infected with Schistosoma mansoni at day 0 and injected with cyclosporin A (CyA) either daily or from day -1 to day 3 were protected against schistosomiasis mansoni as indicated by a decrease in the number of worms recovered from the liver 45 days after infection. CyA treatment also protected rats and strains of mice with known immunity defects (nu/nu, P/N, CBA/N). Protection was evident against both primary and secondary infection in mice infected at day 0, reinfected at day 42, and treated daily with CyA either during the course of the experiment or only from day -1 to day 3, as indicated by the worm burden at day 67. In such an experiment of infection and reinfection, the immature worms were shown to be the target of CyA. Administration of the drug 27, 45, 62, or 100 days before infection confirmed the long-term protective effect of CyA. This drug did not evoke the killing of adult worms in vivo. These data confirm and define the curative and preventive effect of CyA against schistosomiasis mansoni.
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Immune complexes have been detected in the sera of people infected Schistosoma mansoni by the technique of acidification followed by double countercurrent immunoelectrophoresis in hypertonic buffered gels.
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Egyptian subjects living in areas endemic for Schistosoma mansoni or Schistosoma haematobium were selected on the basis of their apparent extremes of resistance or susceptibility to schistosomiasis and examined for T and B cell responses against the major electrophoretically resolved protein species from soluble adult worm extracts. A 42-kDa band was specifically recognized by a significant majority of subjects resistant to schistosomiasis. The 42-kDa species (p-42) from S. mansoni and S. haematobium were immunologically cross-reactive and induced significant protection in mice and hamsters against infection with cercariae. Amino acid sequence analysis of S. mansoni p-42 showed that it consists predominantly of glyceraldehyde 3-P dehydrogenase (G3PDH), which has been shown to be preferentially recognized by the sera of Brazilian subjects resistant to schistosomiasis mansoni. The present data extend the previous findings and imply that S. mansoni-derived G3PDH represents a target of protective T and B cell-mediated antischistosomiasis immunity in humans.
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