Helmut Haas
Bangor University
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Publication
Featured researches published by Helmut Haas.
Journal of Experimental Medicine | 2009
Bart Everts; Georgia Perona-Wright; Hermelijn H. Smits; Cornelis H. Hokke; Alwin J. van der Ham; Colin M. Fitzsimmons; Michael J. Doenhoff; Jürgen van der Bosch; Katja Mohrs; Helmut Haas; Markus Mohrs; Maria Yazdanbakhsh; Gabriele Schramm
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.
Journal of Biological Chemistry | 2003
Gabriele Schramm; Franco H. Falcone; Achim Gronow; Karin Haisch; Uwe Mamat; Michael J. Doenhoff; Guilherme Oliveira; Jürgen Galle; Clemens A. Dahinden; Helmut Haas
The eggs of the parasitic trematodeSchistosoma mansoni are powerful inducers of a T helper type 2 (Th2) immune response and immunoglobulin E (IgE) production.S. mansoni egg extract (SmEA) stimulates human basophils to rapidly release large amounts of interleukin (IL)-4, the key promoter of a Th2 response. Here we show purification and sequence of the IL-4-inducing principle of S. mansoni eggs (IPSE). Stimulation studies with human basophils using SmEA fractions and natural and recombinant IPSE as well as neutralization and immunodepletion studies using antibodies to recombinant IPSE demonstrate that IPSE is the bioactive principle in SmEA leading to activation of basophils and to expression of IL-4 and IL-13. Regarding the mechanism of action, blot analysis showed that IPSE is an IgE-binding factor, suggesting that it becomes effective via cross-linking receptor-bound IgE on basophils. Immunohistology revealed that IPSE is enriched in and secreted from the subshell area of the schistosome egg. We conclude from these data that IPSE may be an important parasite-derived component for skewing the immune response toward Th2.
Journal of Immunology | 2007
Gabriele Schramm; Katja Mohrs; Maren Wodrich; Michael J. Doenhoff; Edward J. Pearce; Helmut Haas; Markus Mohrs
During infection with the helminth parasite Schistosoma mansoni, the deposition of eggs coincides with the onset of IL-4 production and Th2 development. Although IL-4 is known as a potent inducer of Th2 differentiation, the mechanism by which schistosome eggs induce IL-4 production is not clear. In this study, we demonstrate that the S. mansoni egg Ag (SmEA) induces IgE-dependent IL-4 production by basophils derived from Heligmosomoides polygyrus-infected or OVA/alum-immunized mice in the absence of pathogen-specific IgE. The effect is mediated by the secretory glycoprotein IPSE/alpha-1, because IPSE/alpha-1-depleted SmEA no longer induces cytokine production. Conversely, recombinant IPSE/alpha-1 is sufficient to induce IL-4 production. Importantly, the injection of SmEA or recombinant IPSE/alpha-1 into H. polygyrus-infected 4get/KN2 IL-4 reporter mice rapidly induces the dose-dependent IL-4 production by basophils in the liver, a major site of egg deposition. Thus, IPSE/alpha-1 induces basophils to produce IL-4 even in the absence of Ag-specific IgE.
Journal of Experimental Medicine | 2012
Bart Everts; Leonie Hussaarts; Nicole N. Driessen; Moniek H. J. Meevissen; Gabriele Schramm; Alwin J. van der Ham; Barbara van der Hoeven; Thomas Scholzen; Sven Burgdorf; Markus Mohrs; Edward J. Pearce; Cornelis H. Hokke; Helmut Haas; Hermelijn H. Smits; Maria Yazdanbakhsh
Schistosome ribonuclease Omega-1 primes DCs to generate Th2 responses by binding and internalization by the mannose receptor and by subsequently impairing protein synthesis.
European Journal of Immunology | 1999
Helmut Haas; Franco H. Falcone; Gabriele Schramm; Karin Haisch; Bernhard F. Gibbs; Jens Klaucke; Marco Pöppelmann; Wolf-Meinhard Becker; Hans-Joachim Gabius; Max Schlaak
Dietary lectins, present in beans and other edible plant products, pose a potential threat to consumers due to their capacity to induce histamine release from basophils. In this study, we analyzed the capacity of 16 common, in particular dietary, lectins to induce human basophils to secrete IL‐4 and IL‐13, the key promoters of Th2 responses and IgE synthesis. Several of the lectins, especially concanavalin A, lentil lectin, phytohemagglutinin, Pisum sativum agglutinin and Sambucus nigra agglutinin, triggered basophils to release IL‐4 at concentrations of up to 1u2004ngu2009/u2009106 basophils. Lectins with high IL‐4‐inducing capacity also stimulated the release of IL‐13 and histamine. Lectin‐induced IL‐4 and IL‐13 release reached a maximum after 4u2009–u20096u2004h and more than 18u2004h, respectively. Affinoblotting revealed that lectins with the capacity to induce mediator release bind to IgE, suggesting IgE binding as initial step of signal generation. In conclusion, several dietary lectins can trigger human basophils to release IL‐4 and IL‐13. Since lectins can enter the circulation after oral uptake, they might play a role in inducing the so‐called early IL‐4 required to switch the immune response towards a Th2 response and typeu2004I allergy.
FEBS Journal | 2006
Manfred Wuhrer; Crina I. A. Balog; M. I. Catalina; Frances M. Jones; Gabriele Schramm; Helmut Haas; Michael J. Doenhoff; David W. Dunne; André M. Deelder; Cornelis H. Hokke
Schistosomes are parasitic flatworms that infect millions of people in (sub)tropical areas around the world. Glycoconjugates of schistosomes play a critical role in the interaction of the different developmental stages of the parasite with the host. In particular, glycosylated components of the eggs produced by the adult worm pairs living in the bloodstream are strongly immunogenic. We have investigated the glycosylation of interleukin‐4‐inducing factor from schistosome eggs (IPSE/alpha‐1), a major secretory egg antigen from Schistosomau2003mansoni that triggers interleukin‐4 production in human basophils, by MS analysis of tryptic glycopeptides. Nanoscale LC‐MS(/MS) and MALDI‐TOF(/TOF)‐MS studies combined with enzymatic degradations showed that monomeric IPSE/alpha‐1 contains two N‐glycosylation sites, which are each occupied for a large proportion with core‐difucosylated diantennary glycans that carry one or more Lewis X motifs. Lewis X has been reported as a major immunogenic glycan element of schistosomes. This is the first report both on the expression of Lewis X on a specific schistosome egg protein and on a protein‐specific glycosylation analysis of schistosome eggs.
European Journal of Immunology | 2011
Paola Zaccone; Oliver T. Burton; Sarah Gibbs; Nigel Miller; Frances M. Jones; Gabriele Schramm; Helmut Haas; Michael J. Doenhoff; David W. Dunne; Anne Cooke
Immunization with Schistosoma mansoni soluble antigen preparations protects non‐obese diabetic (NOD) mice against the development of type 1 diabetes. These preparations have long been known to induce Th2 responses in vitro and in vivo. Recently, two separate groups have reported that ω‐1, a well‐characterized glycoprotein in S. mansoni soluble egg antigens (SEA), which with IL‐4 inducing principle of S. mansoni eggs (IPSE/α‐1) is one of the two major glycoproteins secreted by live eggs, is a major SEA component responsible for this effect. We found that ω‐1 induces Foxp3 as well as IL‐4 expression when injected in vivo. We confirmed that ω‐1 conditions DCs to drive Th2 responses and further demonstrated that ω‐1 induces Foxp3+ T cells from NOD mouse naïve T cells. In contrast, IPSE/α‐1 did not drive Foxp3 responses. The in vitro development of Foxp3‐expressing T cells by ω‐1 was TGF‐β‐ and retinoic acid‐dependent. Our work, therefore, identifies ω‐1 as an important factor for the induction of Foxp3+ T cells by SEA in NOD mice.
The Journal of Allergy and Clinical Immunology | 1997
Gabriele Schramm; Albrecht Bufe; Arnd Petersen; Helmut Haas; Max Schlaak; Wolf-Meinhard Becker
BACKGROUNDnNew and more successful approaches to diagnosis and therapy of allergic diseases require a more subtle understanding of the structure and the epitopes on the allergen molecule.nnnOBJECTIVEnThis study was done to obtain more information on the structure and the IgE-binding epitopes of a major allergen of velvet grass pollen, Hol l 1.nnnMETHODSnWe cloned Hol l 1 from a complementary DNA library and performed B-cell epitope mapping with 21 recombinant fragments expressed as fusion proteins in Escherichia coli. The fragments were analyzed by Western blotting with sera from 50 different patients.nnnRESULTSnThe patients sera individually recognized at least four different IgE-binding regions (amino acids 1 to 27, 61 to 76, 84 to 105, and 158 to 240). According to their binding patterns with these epitopes, they were divided into five groups. Most sera (92%) bound to the C-terminal peptide (158 to 240), which consists of more than 80 amino acids, whereas there was virtually no binding to smaller fragments covering this region. In contrast to the C-terminal peptide, the IgE-binding peptides on the N terminus and on the middle region of the molecule were of a smaller size (15 to 30 amino acids).nnnCONCLUSIONSnThe major group I allergen of velvet grass bears at least four different IgE-binding epitopes, which were individually recognized by sera from different patients. The C terminus represents the major IgE-binding region and contains at least one discontinuous IgE-binding epitope, whereas the N terminus and middle region of Hol l 1 seem to contain continuous IgE-binding epitopes.
Microbes and Infection | 2010
Gabriele Schramm; Helmut Haas
Schistosoma mansoni eggs - or more specifically, secreted products thereof - are potent inducers of a Th2 response in the host. Here we review current knowledge on the Th2-promoting effects of egg-derived components and the consequences for the host.
Molecular and Biochemical Parasitology | 2009
Gabriele Schramm; J. V. Hamilton; C. I. A. Balog; Manfred Wuhrer; A. Gronow; Svenja Beckmann; Volker Wippersteg; Christoph G. Grevelding; T. Goldmann; E. Weber; Norbert W. Brattig; André M. Deelder; David W. Dunne; Cornelis H. Hokke; Helmut Haas; Michael J. Doenhoff
The major immunopathological consequences of infection with Schistosoma mansoni, a T helper type 2 response and granuloma formation leading to fibrotic tissue damage, are caused by the egg stage of the parasite. Three antigens of S. mansoni eggs, termed IPSE/alpha-1, omega-1 and kappa-5, have been found to be the primary targets of the egg-directed antibody response of the host. Here, we report on the isolation, cloning and characterisation of kappa-5. Apart from an uncharacterised mRNA sequence in S. japonicum, no significant similarities of kappa-5 to known sequences from other species were found. In contrast to IPSE/alpha-1 and omega-1, which have been found only in eggs, kappa-5 was present in miracidia as well as in eggs at the mRNA and protein levels. In eggs, isoforms of kappa-5 were observed with both three and four fully occupied N-glycosylation sites, while in miracidia only one isoform with four N-glycans could be detected. Interestingly, in Western blots sera from S. mansoni-infected Africans were reactive against kappa-5 with IgE and IgG isotype antibodies, but against IPSE/alpha-1 and omega-1 only with IgG antibodies. The further characterisation of kappa-5 as one of the three major egg antigens should help to better understand the immunology and immunopathology of schistosomiasis.