Eosinophil Activity in<i>Schistosoma mansoni</i>Infections In Vivo and In Vitro in Relation to Plasma Cytokine Profile Pre- and Posttreatment with Praziquantel

Reimert, Claus M.; Fitzsimmons, Colin M.; Joseph, Sarah; Mwatha, Joseph K.; Jones, Frances M.; Kimani, Gachuhi; Hoffmann, Karl F.; Booth, Mark; Kabatereine, Narcis B.; Dunne, David W.; Vennervald, Birgitte J.

doi:10.1128/cvi.13.5.584-593.2006

Cited by 32 publications

(27 citation statements)

References 64 publications

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“…However, in the S. mansoni mouse model, although it is induced by IL-12, IL-6 has been shown to downregulate IFN-␥ and IL-12p40 release from lymph node and splenocyte cultures stimulated with anti-CD3 and to induce the production of IL-10 (24), suggesting a regulatory role for this cytokine during S. mansoni infections. In humans, IL-6 is elevated in the sera of individuals who have periportal fibrosis associated with Schistosoma japonicum infection (10), a clinical outcome thought to be due to prolonged anti-inflammatory responses to entrapped eggs, and IL-6, along with IL-5 and IL-10, is elevated in the serum 24 h after treatment with praziquantel, a time point when the plasma TNF-␣ level is significantly decreased compared with pretreatment levels (31). TGF-␤ 1 has been shown to downregulate vaccine-induced in vitro Th1 responses by splenocytes to schistosomulum antigen (45).…”

Section: Discussionmentioning

confidence: 99%

Hepatosplenomegaly Is Associated with Low Regulatory and Th2 Responses to Schistosome Antigens in Childhood Schistosomiasis and Malaria Coinfection

et al. 2008

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Hepatosplenomegaly among Kenyan schoolchildren has been shown to be exacerbated where there is transmission of both Schistosoma mansoni and Plasmodium falciparum. This highly prevalent and chronic morbidity often occurs in the absence of ultrasound-detectable periportal fibrosis and may be due to immunological inflammation. For a cohort of school-age children, whole-blood cultures were stimulated with S. mansoni soluble egg antigen (SEA) or soluble worm antigen (SWA). Responses to SWA were found to be predominantly Th2 cytokines; however, they were not significantly associated with either hepatosplenomegaly or infection with S. mansoni or P. falciparum. In comparison, SEA-specific Th2 cytokine responses were low, and the levels were negatively correlated with S. mansoni infection intensities and were lower among children who were coinfected with P. falciparum. Tumor necrosis factor alpha levels in response to stimulation with SEA were high, and a negative association between presentation with hepatomegaly and the levels of the regulatory cytokines interleukin-6 and transforming growth factor ␤ 1 suggests that a possible mechanism for childhood hepatomegaly in areas where both malaria and schistosomiasis are endemic is poor regulation of an inflammatory response to schistosome eggs.Human schistosomiasis-associated severe pathology, which can result in portal hypertension and hepatosplenomegaly, is the consequence of periportal fibrosis, which is detectable by ultrasonography (33). Periportal fibrosis is thought to result from chronic immunological responses directed against Schistosoma mansoni eggs (12), and since exposure to infection over many years is associated with this pathology (6), it is detected mostly within adult members of populations in areas where S. mansoni is endemic (18,25). However, a form of S. mansoniassociated hepatosplenomegaly that can extend into adulthood is common among children, and the incorporation of ultrasonography into S. mansoni epidemiological studies has shown that this S. mansoni-associated childhood hepatosplenomegaly can occur in the absence of ultrasound-detectable fibrosis (4, 41). It is therefore proposed that immunological inflammation, rather than periportal fibrosis, could be the more common cause of hepatosplenomegaly in this age group (15).Evidence from mouse models suggests that the formation of granulomas around S. mansoni eggs, which are swept by the circulation into the liver, is CD4 ϩ T cell dependent. These CD4 ϩ T cells secrete predominantly Th2 cytokines, and the chronic phase of infection is typified by a continuing, but downregulated, Th2 response (30). In human studies in Brazil, schistosome antigen-specific T-cell clones derived from S. mansoniinfected individuals were found to be predominantly interleukin-4 (IL-4)-secreting CD4 ϩ T cells (9), with mRNA levels indicating that S. mansoni egg antigen (SEA) stimulates a predominantly Th2 response, while S. mansoni worm antigen (SWA) stimulates a nonpolarized Th0 response (44). However, in African studies, bot...

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Section: Discussionmentioning

confidence: 99%

Hepatosplenomegaly Is Associated with Low Regulatory and Th2 Responses to Schistosome Antigens in Childhood Schistosomiasis and Malaria Coinfection

et al. 2008

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“…The drug is safe and has a high efficacy against both trematodes and cestodes (9,11). Furthermore, there is evidence that treatment with praziquantel induces a change in the immune response that provides partial protection against schistosome infection, thus providing benefits that may extend beyond a transient reduction in levels of infection (21,40,42). Additionally, although the cumulative fibrosis that occurs during infection is mostly irreversible, periportal fibrosis regresses following eradication of the infection by chemotherapy (16,44,48).…”

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confidence: 99%

Effect of Chemotherapy with Praziquantel on the Production of Cytokines and Morbidity Associated with Schistosomiasis Mansoni

Martins-Leite

Gazzinelli

Alves-Oliveira

et al. 2008

Antimicrob Agents Chemother

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The objective of the present study was to test the hypothesis that treatment of schistosomiasis mansoni with praziquantel can alter significantly the immune response of patients and generate a reversal of the level of fibrosis. Peripheral blood mononuclear cell (PBMC) samples were collected from, and abdominal ultrasound examinations conducted on, volunteers infected with Schistosoma mansoni and living in an area where the disease is endemic, both prior to and one year after treatment with praziquantel. Subjects were classified into groups according to the level of pathology (i.e., absent, incipient, moderate, or severe fibrosis). PBMCs were stimulated with schistosome soluble egg antigens (SEA), and the levels of production of the cytokines gamma interferon (IFN-␥), tumor necrosis factor alpha, transforming growth factor ␤, and interleukin-4 (IL-4), IL-10, and IL-13 were determined. The chemotherapy was effective in reducing morbidity, particularly for individuals presenting with severe fibrosis. When levels of cytokine production in posttreatment PBMC cultures stimulated by SEA were categorized as low or high, significant differences in the distribution of IL-13 levels between groups presenting with or not presenting with fibrosis were established. Comparison of pre-and posttreatment SEA-induced cytokine levels in individuals who had experienced no change in the grade of fibrosis following chemotherapy revealed that the level of IFN-␥ decreased in subjects with fibrosis whereas that of IL-10 decreased in individuals with and without fibrosis. The data suggest that chemotherapy is effective in reducing the morbidity of the disease and that the level of IL-13 may be a useful indicator of the persistence of fibrosis following treatment.

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“…Bearing in mind that schistosomiasis is a disease caused by intravascular worms, inhibition of active basophil degranulation may be necessary to prevent excessive allergic-like responses in the bloodstream. Interestingly, suppression of basophil function may be vital during PZQ treatment, which induces a massive allergic-like response upon the death of adult worms, with relatively few clinical symptoms (8, 62). …”

Section: 0 Discussionmentioning

confidence: 99%

Immuno-evasive tactics by schistosomes identify an effective allergy preventative

Griffith

Liang

Whitworth

et al. 2015

Experimental Parasitology

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Many chronic inflammatory diseases can be improved by helminth infection, but the mechanisms are poorly understood. Allergy and helminthiasis are both associated with Th2-like immune responses; thus, defining how infection with parasites leads to reduced allergy has been particularly challenging. We sought to better understand this conundrum by evaluating host-parasite interactions involved in Th2 immunity in human schistosomiasis. Immune cells were cultured with schistosomes and the effect on CD23, an IgE receptor associated with resistance in schistosomiasis, was evaluated. Cells treated with schistosomes demonstrated reduced surface CD23 levels with a parallel accumulation of soluble (s) CD23 suggesting this IgE receptor is proteolytically cleaved by the parasite. Consistent with this hypothesis, a schistosome-generated (SG)-sCD23 fragment of 15kDa was identified. SG-sCD23 inhibited IgE from binding to CD23 and FcεRI, but lacked the ability to bind CD21. These results suggested that schistosomes target IgE-mediated immunity in immuno-evasive tactics. Based on its characteristics, we predicted that SG-sCD23 would function as an efficacious allergy preventative. Treatment of human FcεRI-transgenic mice with recombinant (r) SG-sCD23 reduced the ability of human IgE to induce an acute allergic response in vivo. In addition, an optimized form of rSG-sCD23 with an introduced point mutation at Asp258 (D258E) to stabilize IgE binding had increased efficacy compared to native rSG-sCD23. Schistosome infection may thus inhibit allergic-like protective immune responses by increasing soluble IgE decoy receptors. Allergy treatments based on this naturally occurring phenomenon may be highly effective and have fewer side effects with long-term use.

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Eosinophil Activity inSchistosoma mansoniInfections In Vivo and In Vitro in Relation to Plasma Cytokine Profile Pre- and Posttreatment with Praziquantel

Cited by 32 publications

References 64 publications

Hepatosplenomegaly Is Associated with Low Regulatory and Th2 Responses to Schistosome Antigens in Childhood Schistosomiasis and Malaria Coinfection

Hepatosplenomegaly Is Associated with Low Regulatory and Th2 Responses to Schistosome Antigens in Childhood Schistosomiasis and Malaria Coinfection

Effect of Chemotherapy with Praziquantel on the Production of Cytokines and Morbidity Associated with Schistosomiasis Mansoni

Immuno-evasive tactics by schistosomes identify an effective allergy preventative

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