Cytokine Production Associated with Periportal Fibrosis during Chronic Schistosomiasis Mansoni in Humans

Oliveira, Lúcia Fraga Alves; Moreno, Elizabeth Castro; Gazzinelli, Giovanni; Martins‐Filho, Olindo Assis; Silveira, Alda Maria Soares; Gazzinelli, Andréa; Malaquias, Luiz Cosme Cotta; LoVerde, Philip T.; Leite, Pauline Martins; Corrêa-Oliveira, Rodrigo

doi:10.1128/iai.74.2.1215-1221.2006

Cited by 85 publications

(97 citation statements)

References 36 publications

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“…2A, C, and E). These dose response data are comparable to those reported for studies of SEA stimulation of professional immune cells (28)(29)(30)(31) and informed our selection of an SEA dose of 25 g/ml for 24 h.…”

Section: Resultssupporting

confidence: 78%

Schistosome Egg Antigens Elicit a Proinflammatory Response by Trophoblast Cells of the Human Placenta

et al. 2013

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f Schistosomiasis affects nearly 40 million women of reproductive age. Many of these women are infected while pregnant and lactating. Several studies have demonstrated transplacental trafficking of schistosome antigens; however, little is known regarding how these antigens affect the developing fetus and placenta. To evaluate the impact of schistosomiasis on trophoblasts of the human placenta, we isolated primary trophoblast cells from healthy placentas delivered at term. These trophoblasts were placed in culture and treated with Schistosoma japonicum soluble egg antigens (SEA) or plasma from S. japonicum-infected pregnant women. Outcomes measured included cytokine production and activation of signal transduction pathways. Treatment of primary human trophoblast cells with SEA resulted in upregulation of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8 and the chemokine macrophage inflammatory protein 1␣ (MIP-1␣). Cytokine production in response to SEA was dose dependent and reminiscent of production in response to other proinflammatory stimuli, such as Toll-like receptor 2 (TLR2) and TLR4 agonists. In addition, the signaling pathways extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal protein kinase (JNK), p38, and NF-B were all activated by SEA in primary trophoblasts. These effects appeared to be mediated through both carbohydrate and protein epitopes of SEA. Finally, primary trophoblasts cocultured with plasma from S. japonicum-infected pregnant women produced increased levels of IL-8 compared to trophoblasts cocultured with plasma from uninfected pregnant women. We report here a direct impact of SEA on primary human trophoblast cells, which are critical for many aspects of a healthy pregnancy. Our data indicate that schistosome antigens can activate proinflammatory responses in trophoblasts, which might compromise maternal-fetal health in pregnancies complicated by schistosomiasis.

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Section: Resultssupporting

confidence: 78%

Schistosome Egg Antigens Elicit a Proinflammatory Response by Trophoblast Cells of the Human Placenta

et al. 2013

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“…3,4 Upstream of the TH2 pathway, IL-10 is implicated in negotiating the balance between TH1 and TH2 immunity, involving a third class of T reg cells. 5,6 During chronic schistosomiasis infection, IL-10 production also reduces collateral tissue damage and TH2-induced fibrosis in the liver [7][8][9][10] in response to deposition of S. mansoni eggs. 4 In addition to have a function in host defense against helminthic infection, the TH2 pathway is pathologically activated in atopic diseases (including asthma) in response to stimulus by environmental allergens.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population

et al. 2010

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Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopyrelated IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P ¼ 0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P ¼ 0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.

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“…Within areas where the disease is highly endemic, most of the infected subjects control the infection with only minor pathological manifestations. However, in a small percentage of infected individuals, extended periportal fibrosis leads to portal hypertension, varices or ascites, the incidence of which has been found to correlate with the age and gender of the subject and the intensity of infection (2,5,7).…”

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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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Cytokine Production Associated with Periportal Fibrosis during Chronic Schistosomiasis Mansoni in Humans

Cited by 85 publications

References 36 publications

Schistosome Egg Antigens Elicit a Proinflammatory Response by Trophoblast Cells of the Human Placenta

Schistosome Egg Antigens Elicit a Proinflammatory Response by Trophoblast Cells of the Human Placenta

Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population

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

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