<i>Schistosoma mansoni</i> schistosomula antigens induce Th1/Pro‐inflammatory cytokine responses

Egesa, Moses; Lubyayi, Lawrence; Tukahebwa, Edridah M.; Bagaya, Bernard S.; Chalmers, Iain W.; Wilson, Shona; Hokke, Cornelis H.; Hoffmann, Karl F.; Dunne, David W.; Yazdanbakhsh, Maria; Labuda, Lucja A.; Cose, Stephen

doi:10.1111/pim.12592

Cited by 19 publications

(17 citation statements)

References 54 publications

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“…The failure to develop effective vaccines may be due to a variety of factors, including the fact that the current understanding of schistosomiasis immunity and immune mechanisms is largely dependent on studies in mice, but vaccines conducted in studies only in mouse models may have undesirable effects in human clinical trials. A vigorous humoral response (IgG, IgM, and IgE) is found in patients with acute and chronic schistosomiasis, which is different from that in mice [7,27,28]. Therefore, new Schistosome vaccine molecules and vaccination are still needed for study.…”

Section: Discussionmentioning

confidence: 99%

An Efficient Schistosoma japonicum Bivalent Membrane Protein Antigen DNA Vaccine Against Schistosomiasis in Mice

et al. 2019

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BackgroundSchistosomiasis is one of the most important infectious parasitic diseases in the world. The most important was to control schistosomiasis is through a combination of medical therapy and immunization. The membrane antigens Tsp2 and 29 from Schistosoma are promising anti-schistosomiasis vaccine candidates.Material/MethodsIn this study, the pcDNA3.1(+)-SjTsp2, pcDNA3.1(+)-Sj29, and pcDNA3.1 (+)-SjTsp2-29 eukaryotic expression vectors were successfully constructed as DNA vaccines, and the protective abilities of these vaccines were evaluated in mice.ResultsThe results showed that vaccination with SjTsp2, Sj29, and SjTsp2-29 reduced parasite burden and hepatic pathology compared to the control group, and the protective effect of the bivalent SjTsp2-29 DNA vaccine was better than that of the univalent SjTsp2 or Sj29 DNA vaccines. We also found high levels of IgG, IgG1, and IgG2a against SjTsp2, Sj29, and SjTsp2-29 DNA vaccines, with high expression of IFN-γ and no IL-4 in the mice.ConclusionsThe double-membrane antigen DNA vaccine SjTsp2-29 elicited protection against Schistosoma infection and might serve as a vaccine candidate.

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Section: Discussionmentioning

confidence: 99%

An Efficient Schistosoma japonicum Bivalent Membrane Protein Antigen DNA Vaccine Against Schistosomiasis in Mice

et al. 2019

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“…IPSE/α1 induces a mixed Th1/Th2 response and promote the development of hepatic granuloma (19), while lacto-N-fucopentaose III and ω1 directly act on dendritic cells (DCs) to enhance the Th2 response (21,24). In addition, Th1type responses could also be induced by the schistosome vaccine candidates MAP4 (25), egg-derived r38 (22,26), rSmLy6B, rSmTSP6, and rSmTSP7 (27), and rSjCRT (28).…”

Section: The Role Of Th1/th2 Responses In the Immunopathology Of Schimentioning

confidence: 99%

T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

et al. 2020

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The parasitic worms, Schistosoma mansoni and Schistosoma japonicum, reside in the mesenteric veins, where they release eggs that induce a dramatic granulomatous response in the liver and intestines. Subsequently, infection may further develop into significant fibrosis and portal hypertension. Over the past several years, uncovering the mechanism of immunopathology in schistosomiasis has become a major research objective. It is known that T lymphocytes, especially CD4 + T cells, are essential for immune responses against Schistosoma species. However, obtaining a clear understanding of how T lymphocytes regulate the pathological process is proving to be a daunting challenge. To date, CD4 + T cell subsets have been classified into several distinct T helper (Th) phenotypes including Th1, Th2, Th17, T follicular helper cells (Tfh), Th9, and regulatory T cells (Tregs). In the case of schistosomiasis, the granulomatous inflammation and the chronic liver pathology are critically regulated by the Th1/Th2 responses. Animal studies suggest that there is a moderate Th1 response to parasite antigens during the acute stage, but then, egg-derived antigens induce a sustained and dominant Th2 response that mediates granuloma formation and liver fibrosis. In addition, the newly discovered Th17 cells also play a critical role in the hepatic immunopathology of schistosomiasis. Within the liver, Tregs are recruited to hepatic granulomas and exert an immunosuppressive role to limit the granulomatous inflammation and fibrosis. Moreover, recent studies have shown that Tfh and Th9 cells might also promote liver granulomas and fibrogenesis in the murine schistosomiasis. Thus, during infection, T-cell subsets undergo complicated cross-talk with antigen presenting cells that then defines their various roles in the local microenvironment for regulating the pathological progression of schistosomiasis. This current review summarizes a vast body of literature to elucidate the contribution of T lymphocytes and their associated cytokines in the immunopathology of schistosomiasis.

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“…Immune responses to penetrating and migrating Schistosoma larvae (schistosomula) and maturing adults are predominantly T h 1 ( 26 ). Excretory/secretory Schistosoma antigens damage host barrier cells which release alarmins, activate innate cells and induce proinflammatory cytokines (IL1B, IL6, IL17, TNF, and IFNG) ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

The Genetics of Human Schistosomiasis Infection Intensity and Liver Disease: A Review

et al. 2021

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Schistosomiasis remains the fourth most prevalent parasitic disease affecting over 200 million people worldwide. Control efforts have focussed on the disruption of the life cycle targeting the parasite, vector and human host. Parasite burdens are highly skewed, and the majority of eggs are shed into the environment by a minority of the infected population. Most morbidity results from hepatic fibrosis leading to portal hypertension and is not well-correlated with worm burden. Genetics as well as environmental factors may play a role in these skewed distributions and understanding the genetic risk factors for intensity of infection and morbidity may help improve control measures. In this review, we focus on how genetic factors may influence parasite load, hepatic fibrosis and portal hypertension. We found 28 studies on the genetics of human infection and 20 studies on the genetics of pathology in humans. S. mansoni and S. haematobium infection intensity have been showed to be controlled by a major quantitative trait locus SM1, on chromosome 5q31-q33 containing several genes involved in the Th2 immune response, and three other loci of smaller effect on chromosomes 1, 6, and 7. The most common pathology associated with schistosomiasis is hepatic and portal vein fibroses and the SM2 quantitative trait locus on chromosome six has been linked to intensity of fibrosis. Although there has been an emphasis on Th2 cytokines in candidate gene studies, we found that four of the five QTL regions contain Th17 pathway genes that have been included in schistosomiasis studies: IL17B and IL12B in SM1, IL17A and IL17F in 6p21-q2, IL6R in 1p21-q23 and IL22RA2 in SM2. The Th17 pathway is known to be involved in response to schistosome infection and hepatic fibrosis but variants in this pathway have not been tested for any effect on the regulation of these phenotypes. These should be priorities for future studies.

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Schistosoma mansoni schistosomula antigens induce Th1/Pro‐inflammatory cytokine responses

Cited by 19 publications

References 54 publications

An Efficient Schistosoma japonicum Bivalent Membrane Protein Antigen DNA Vaccine Against Schistosomiasis in Mice

An Efficient Schistosoma japonicum Bivalent Membrane Protein Antigen DNA Vaccine Against Schistosomiasis in Mice

T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

The Genetics of Human Schistosomiasis Infection Intensity and Liver Disease: A Review

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