The identification and characterization of new immunogenic egg components: implications for evaluation and control of the immunopathogenic T cell response in schistosomiasis

Stadecker, Miguel J.; Hernández, Héctor J.; Asahi, Hiroko

doi:10.1590/s0074-02762001000900004

Cited by 27 publications

(22 citation statements)

References 32 publications

(17 reference statements)

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“…To date, only a handful of ESP and SEA components have been characterized. One of the most abundant egg proteins comprising 10% of total SEA is Schistosoma mansoni 40 kDa protein (Sm-p40, [14]), a protein with homology to small heat shock proteins (HSPs) and α-crystallin [15]. By examining the ability of SEA fractions to stimulate proliferation of CD4 + Th cells isolated from S. mansoni infected mice, not only Sm-p40, but p150/166 (albumin), phosphoenolpyruvate carboxykinase, glutathione S-transferase (GST)-(28K), peroxiredoxin 1, and SmEP25 [16] proteins have been identified.…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of Schistosoma mansoni egg secretions

Cass

Johnson

Califf

et al. 2007

Molecular and Biochemical Parasitology

190

189

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Schistosomiasis remains a largely neglected, global health problem. The morbid pathology of the disease stems from the host's inflammatory response to parasite eggs trapped in host tissues. Long term host/parasite survival is dependent upon the successful modulation of the acute pathological response, which is induced by egg antigens. In this study, using Multidimensional Protein Identification Technology, we identified the Schistosoma mansoni egg secretome consisting of 188 proteins. Notably we identified proteins involved in redox balance, molecular chaperoning and protein folding, development and signaling, scavenging and metabolic pathways, immune response modulation, and 32 novel, previously uncharacterized schistosome proteins. We localized a subset of previously-characterized schistosome proteins identified in egg secretions in this study, to the surface of live S. mansoni eggs using the circumoval precipitin reaction. The identification of proteins actively secreted by live schistosome eggs provides important new information for understanding immune modulation and the pathology of schistosomiasis.

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Section: Introductionmentioning

confidence: 99%

Proteomic analysis of Schistosoma mansoni egg secretions

Cass

Johnson

Califf

et al. 2007

Molecular and Biochemical Parasitology

190

189

View full text Add to dashboard Cite

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“…Interestingly, in the low pathology BL/6 strain, an initial, short-lived Th1-type cytokine response to a soluble schistosome egg Ag preparation (SEA) 5 readily yields to a Th2-dominated response (13,14), whereas in the high pathology CBA strain the early Th1 response lingers alongside the developing Th2 response (15). Moreover, CBA and C3H high pathology mice display a prominent CD4 ϩ T cell response against the major Sm-p40 egg Ag (16), whereas low pathology BL/6 mice do not, and preferentially react to other SEA components (17).…”

mentioning

confidence: 99%

Apoptosis by Neglect of CD4+ Th Cells in Granulomas: A Novel Effector Mechanism Involved in the Control of Egg-Induced Immunopathology in Murine Schistosomiasis

Rutitzky

Mirkin

Stadecker

2003

The Journal of Immunology

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In infection with Schistosoma mansoni, parasite eggs precipitate an intrahepatic granulomatous and fibrosing inflammation that is mediated by CD4+ Th cells. Compared with CBA mice, C57BL/6 mice develop smaller granulomas composed of cells that exhibit reduced proliferative responses to schistosome egg Ags. In the present study, we investigated CD4+ T cell apoptosis as a possible mechanism that could account for this subdued response. We found throughout the course of several infection weeks a markedly higher proportion of apoptotic CD4+ T cells in granulomas from C57BL/6 mice than in those from CBA mice ex vivo; the apoptosis further increased upon cell cultivation in vitro. Activation-induced cell death or CD8+ T cells failed to account for the enhanced apoptosis as infected Fas-, Fas ligand,- and CD8-deficient mice exhibited similar apoptosis to that seen in wild-type counterparts. However, a strikingly lower IL-2 production by schistosome egg Ag-stimulated C57BL/6 granuloma and mesenteric lymph node cells suggested the possibility of apoptosis due to growth factor deprivation. Indeed, the CD4+ T cell apoptosis was significantly reversed by addition of rIL-2 in vitro, or by injection of rIL-2 in vivo, which also resulted in significant exacerbation of granulomatous inflammation. These findings indicate that apoptosis by neglect can represent a significant means of controlling CD4+ T cells that mediate the immunopathology in schistosomiasis.

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“…In murine schistosomiasis, Hernandez et al (1998) reported that the cells responding to Smp40 antigen secreted high level of IFN-γ. These different findings in the different model introduce the important notion that egg antigens can vary significantly in immunogenicity according to the host's genetic background (Stadecker et al 2001).…”

Section: Discussionmentioning

confidence: 95%

Schistosoma mansoni major egg antigen Smp40: molecular modeling and potential immunoreactivity for anti-pathology vaccine development

Abouel-Nour

Lotfy²,

Attallah³

et al. 2006

Mem. Inst. Oswaldo Cruz

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The pathogenesis of Schistosoma mansoni infection is largely determined by host T-cell mediated immuneSchistosomiasis is a debilitating parasitic disease affecting about 200 million people in 70 countries in the world and is caused by one of the three different species of Schistosoma: S. mansoni, S. haematobium, and S. japonicum. The major pathology of these parasitic infections is associated with a host delayed type hypersensitivity reaction to parasitic egg and egg products. Granulomatous inflammation is a cellular hypersensitivity reaction mediated by egg antigen-specific, MHC class II-restricted, TCR αβ expressing, CD4 + T helper cells (Iacomini et al. 1995). Patients infected with S. mansoni mount cellular and humoral immune responses to soluble egg antigens derived from crude homogenates of eggs. Thus, the end result of host responses to schistosome eggs in the liver is advanced portal fibrosis with dense deposits of collagens in greatly expanded portal tracts (El-Zayadi 2004). The immune reaction produced by the body against the schistosomal infection is a double-weaponed arm. Unfortunately, the harmful weapon is the longest and the most powerful. That is the immune reaction against the schistosomal egg causing the schistosomal granuloma. The other weapon of the immune system that should be lengthened and empowered is the protective immune response against infection, egg production and/or the granuloma formation. Many researchers have been doing their best to get the suitable agent that can stimulate the maximal, specific immune response against schistosomiasis (Goes & Hirsch 1996).Considerable efforts have been exerted to determine which S. mansoni antigens induce and elicit T cell-mediated responses and granuloma formation (Goes & Hirsch 1996). Several laboratories have isolated various antigens from crude soluble egg anigens (SEA) and soluble worm antigens (SWAP), and investigated their role in serology, blastogenic reactions, and granuloma responses to SEA (Bahia-Oliveira et al. 1997). These studies revealed a variety of biologically active antigenic moeities derived from S. mansoni antigen preparations (Goes & Hirsch 1996). One antigen, Smp40 (major egg antigen p40), has been described as highly immunogenic in humans and has been cloned and sequenced (Cao et al. 1993). The Smp40 peptide has 354 amino acid residues and shares homologies with the family of heat shock proteins and α-crystallins. There is evidence that α-crystallins act as chaperone for other important egg antigens released during the migra- tion phase of the eggs in the hepatic system (Nene et al. 1986). The immune response to Smp40 and Smp40 overlapping peptides can be studied in the cellular proliferation assays with the addition of either anti-interleukin (IL)-10 or IL-2 to overcome anergy. In the last decade, substantial resources have been invested to identify, characterize, and purify various schistosome antigens for the purpose of designing and testing potential vaccines. In fact, elucidation of egg antigens has received much les...

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The identification and characterization of new immunogenic egg components: implications for evaluation and control of the immunopathogenic T cell response in schistosomiasis

Cited by 27 publications

References 32 publications

Proteomic analysis of Schistosoma mansoni egg secretions

Proteomic analysis of Schistosoma mansoni egg secretions

Apoptosis by Neglect of CD4+ Th Cells in Granulomas: A Novel Effector Mechanism Involved in the Control of Egg-Induced Immunopathology in Murine Schistosomiasis

Schistosoma mansoni major egg antigen Smp40: molecular modeling and potential immunoreactivity for anti-pathology vaccine development

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