Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses

Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. mansoni egg antigen [SEA]) induce strong Th2 responses both in vitro and in vivo. However, the specific molecules that prime the development of Th2 responses have not been identified. We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA. Furthermore, using IL-4 dual reporter mice, we show that both natural and recombinant omega-1 alone are sufficient to generate Th2 responses in vivo, even in the absence of IL-4R signaling. Finally, omega-1–depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1–mediated effects. Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses.

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The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1)

Journal of Experimental Medicine ◽

10.1084/jem.20082462 ◽

2009 ◽

Vol 206 (8) ◽

pp. 1681-1690 ◽

Cited By ~ 213

Author(s):

Svenja Steinfelder ◽

John F. Andersen ◽

Jennifer L. Cannons ◽

Carl G. Feng ◽

Manju Joshi ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Lymphocytes ◽

Interleukin 4 ◽

Native Protein ◽

Egg Extract ◽

Th2 Polarization ◽

Th2 Responses

Schistosoma mansoni eggs contain factors that trigger potent Th2 responses in vivo and condition mouse dendritic cells (DCs) to promote Th2 lymphocyte differentiation. Using an in vitro bystander polarization assay as the readout, we purified and identified the major Th2-inducing component from soluble egg extract (SEA) as the secreted T2 ribonuclease, omega-1. The Th2-promoting activity of omega-1 was found to be sensitive to ribonuclease inhibition and did not require MyD88/TRIF signaling in DCs. In common with unfractioned SEA, the purified native protein suppresses lipopolysaccharide-induced DC activation, but unlike SEA, it fails to trigger interleukin 4 production from basophils. Importantly, omega-1–exposed DCs displayed pronounced cytoskeletal changes and exhibited decreased antigen-dependent conjugate formation with CD4+ T cells. Based on this evidence, we hypothesize that S. mansoni omega-1 acts by limiting the interaction of DCs with CD4+ T lymphocytes, thereby lowering the strength of the activation signal delivered.

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Faculty Opinions recommendation of Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1018413.209475 ◽

2004 ◽

Author(s):

Paul J Brindley

Keyword(s):

Schistosoma Mansoni ◽

Praziquantel Treatment

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Enhancing the Nrf2 Antioxidant Signaling Provides Protection Against Trichloroethene-mediated Inflammation and Autoimmune Response

Toxicological Sciences ◽

10.1093/toxsci/kfaa022 ◽

2020 ◽

Vol 175 (1) ◽

pp. 64-74 ◽

Cited By ~ 3

Author(s):

Nivedita Banerjee ◽

Hui Wang ◽

Gangduo Wang ◽

M Firoze Khan

Keyword(s):

Oxidative Stress ◽

T Cells ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Autoimmune Response ◽

Mediated Effects ◽

Antioxidant Gene Expression ◽

Responsive Element

Abstract Trichloroethene (trichloroethylene, TCE) and one of its reactive metabolites dichloroacetyl chloride (DCAC) are associated with the induction of autoimmunity in MRL+/+ mice. Although oxidative stress plays a major role in TCE-/DCAC-mediated autoimmunity, the underlying molecular mechanisms still need to be delineated. Nuclear factor (erythroid-derived 2)-like2 (Nrf2) is an oxidative stress-responsive transcription factor that binds to antioxidant responsive element (ARE) and provides protection by regulating cytoprotective and antioxidant gene expression. However, the potential of Nrf2 in the regulation of TCE-/DCAC-mediated autoimmunity is not known. This study thus focused on establishing the role of Nrf2 and consequent inflammatory responses in TCE-/DCAC-mediated autoimmunity. To achieve this, we pretreated Kupffer cells (KCs) or T cells with/without tert-butylhydroquinone (tBHQ) followed by treatment with DCAC. In both KCs and T cells, DCAC treatment significantly downregulated Nrf2 and HO-1 expression along with induction of Keap-1 and caspase-3, NF-κB (p65), TNF-α, and iNOS, whereas pretreatment of these cells with tBHQ attenuated these responses. The in vitro findings were further verified in vivo by treating female MRL+/+ mice with TCE along with/without sulforaphane. TCE exposure in mice also led to reduction in Nrf2 and HO-1 but increased phospho-NF-κB (p-p65) and iNOS along with increased anti-dsDNA antibodies. Interestingly, sulforaphane treatment led to amelioration of TCE-mediated effects, resulting in Nrf2 activation and reduction in inflammatory and autoimmune responses. Our results show that TCE/DCAC mediates an impairment in Nrf2 regulation. Attenuation of TCE-mediated autoimmunity via activation of Nrf2 supports that antioxidants sulforaphane/tBHQ could be potential therapeutic agents for autoimmune diseases.

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In vitro and in vivo studies of the effect of artemether on Schistosoma mansoni.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.33.9.1557 ◽

1989 ◽

Vol 33 (9) ◽

pp. 1557-1562 ◽

Cited By ~ 93

Author(s):

S H Xiao ◽

B A Catto

Keyword(s):

Schistosoma Mansoni ◽

In Vivo Studies

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Niosomes for enhanced activity of praziquantel against Schistosoma mansoni: in vivo and in vitro evaluation

Parasitology Research ◽

10.1007/s00436-018-6132-z ◽

2018 ◽

Vol 118 (1) ◽

pp. 219-234 ◽

Cited By ~ 4

Author(s):

Hager S. Zoghroban ◽

Samy I. El-Kowrany ◽

Ibrahim A. Aboul Asaad ◽

Gamal M. El Maghraby ◽

Kholoud A. El-Nouby ◽

...

Keyword(s):

Schistosoma Mansoni ◽

In Vitro Evaluation ◽

Enhanced Activity

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The N-terminus moiety of the cystatin SmCys from Schistosoma mansoni regulates its inhibitory activity in vitro and in vivo

Molecular and Biochemical Parasitology ◽

10.1016/j.molbiopara.2003.10.016 ◽

2004 ◽

Vol 134 (1) ◽

pp. 65-73 ◽

Cited By ~ 19

Author(s):

Fabiana Carvalho Morales ◽

Daniel Rodrigues Furtado ◽

Franklin David Rumjanek

Keyword(s):

Schistosoma Mansoni ◽

Inhibitory Activity ◽

N Terminus

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Inhibition of in vitro macrophage-induced low density lipoprotein oxidation by thyroid compounds

Journal of Endocrinology ◽

10.1677/joe.0.1770137 ◽

2003 ◽

Vol 177 (1) ◽

pp. 137-146 ◽

Cited By ~ 11

Author(s):

L Oziol ◽

P Faure ◽

N Bertrand ◽

P Chomard

Keyword(s):

Cell Viability ◽

Antioxidant Capacity ◽

Density Lipoprotein ◽

Thiobarbituric Acid ◽

Human Monocyte ◽

Ldl Oxidation ◽

Low Density ◽

Redox Systems

Oxidized low density lipoproteins (LDL) are highly suspected of initiating the atherosclerosis process. Thyroid hormones and structural analogues have been reported to protect LDL from lipid peroxidation induced by Cu2+ or the free radical generator 2,2'-azobis-'2-amidinopropane' dihydrochloride in vitro. We have examined the effects of thyroid compounds on macrophage-induced LDL oxidation. Human monocyte-derived macrophages (differentiated U937 cells) were incubated for 24 h with LDL and different concentrations (0-20 microM) of 3,5,3'-triiodo-l -thyronine (T3), 3,5,3',5'-tetraiodo-L-thyronine (T4), 3,3',5'-tri-iodo-l -thyronine (rT3), the T3 acetic derivative (3,5,3'-tri-iodothyroacetic acid; TA3) or L-thyronine (T0) (experiment 1). Cells were also preincubated for 24 h with 1 or 10 microM of the compounds, washed twice, then incubated again for 24 h with LDL (experiment 2). Oxidation was evaluated by measurement of thiobarbituric acid-reactive substances (TBARS) and cell viability by lactate deshydrogenase release. In experiment 1, T0 had no effect, whereas the other compounds decreased LDL TBARS production, but T3 and TA3 were less active than T4 and rT3 (IC50: 11.0 +/- 2.6 and 8.1 +/- 0.8 vs 1.4 +/- 0.5 and 0.9 +/- 0.3 microM respectively). In experiment 2, the compounds at 1 microM had no effect; at 10 microM, T3 and rT3 slightly reduced LDL TBARS production, whereas TA3 and T4 inhibited it by about 50% and 70% respectively. TBARS released by the cells were also highly decreased by T3, T4, rT3 and TA3 in experiment 1, but only by T3 (30%) and T4 (70%) in experiment 2. Cell viability was not affected by the compounds except slightly by TA3 at 10 microM. The data suggested that the physico-chemical antioxidant capacity of thyroid compounds was modulated by their action on the intracellular redox systems of macrophage. Overall cellular effects of T3 led to a reduction of its antioxidant capacity whereas those of T4 increased it. Thus T4 might protect LDL against cellular oxidation in vivo more than T3.

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