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4. Inverse Correlation of Th2-Specific Cytokines with Hepatic Egg Burden in S. mansoni -Infected Hamsters.

Author

Russ, Lena, von Bülow, Verena, Wrobel, Sarah, Stettler, Frederik, Schramm, Gabriele, Falcone, Franco H., Grevelding, Christoph G., Roderfeld, Martin, and Roeb, Elke

Subjects
STATISTICAL correlation, PARASITIC diseases, GASTROINTESTINAL system, INVERSE relationships (Mathematics), IMMUNE response
Abstract

Schistosomiasis, a parasitic disease caused by Schistosoma spp., affects more than 250 million people worldwide. S. mansoni in particular affects the gastrointestinal tract and, through its eggs, induces a Th2 immune response leading to granuloma formation. The relationship between egg load and immune response is poorly understood. We investigated whether the quantity of parasitic eggs influences the immune response in S. mansoni-infected hamsters. The hepatic and intestinal egg load was assessed, and cytokine expression as well as the expression of three major egg-derived proteins were analyzed in monosex- and bisex-infected animals by qRT-PCR. Statistical correlations between egg load or egg-derived factors Ipse/alpha-1, kappa-5, and omega-1, and the immune response were analyzed in liver and colon tissue. Surprisingly, no correlation of the Th1 cytokines with the hepatic egg load was observed, while the Th2 cytokines Il4, Il5, and Il13 showed an inverse correlation in the liver but not in the colon. A longer embryogenesis of the parasitic eggs in the liver could explain this correlation. This conclusion is supported by the lack of any correlation with immune response in the colon, as the intestinal passage of the eggs is limited to a few days. [ABSTRACT FROM AUTHOR]

Published
2024
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9. IPSE, an abundant egg-secreted protein of the carcinogenic helminth Schistosoma haematobium, promotes proliferation of bladder cancer cells and angiogenesis

Author

Mbanefo, Evaristus C., Agbo, Chinwike Terry, Zhao, Yuanlong, Lamanna, Olivia K., Thai, Kim H., Karinshak, Shannon E., Khan, Mohammad Afzal, Fu, Chi-Ling, Odegaard, Justin I., Saltikova, Irina V., Smout, Michael J., Pennington, Luke F., Nicolls, Mark R., Jardetzky, Theodore S., Loukas, Alex, Brindley, Paul J., Falcone, Franco H., and Hsieh, Michael H.

Published
2020
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12. Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases

Author

Metcalfe, Dean D., Pawankar, Ruby, Ackerman, Steven J., Akin, Cem, Clayton, Frederic, Falcone, Franco H., Gleich, Gerald J., Irani, Anne-Marie, Johansson, Mats W., Klion, Amy D., Leiferman, Kristin M., Levi-Schaffer, Francesca, Nilsson, Gunnar, Okayama, Yoshimichi, Prussin, Calman, Schroeder, John T., Schwartz, Lawrence B., Simon, Hans-Uwe, Walls, Andrew F., and Triggiani, Massimo

Published
2016
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15. Metabolic reprogramming of hepatocytes by Schistosoma mansoni eggs

Author

von Bülow, Verena, primary, Gindner, Sarah, additional, Baier, Anne, additional, Hehr, Laura, additional, Buss, Nicola, additional, Russ, Lena, additional, Wrobel, Sarah, additional, Wirth, Victoria, additional, Tabatabai, Kuscha, additional, Quack, Thomas, additional, Haeberlein, Simone, additional, Kadesch, Patrik, additional, Gerbig, Stefanie, additional, Wiedemann, Katja R., additional, Spengler, Bernhard, additional, Mehl, Annabel, additional, Morlock, Gertrud, additional, Schramm, Gabriele, additional, Pons-Kühnemann, Jörn, additional, Falcone, Franco H., additional, Wilson, R. Alan, additional, Bankov, Katrin, additional, Wild, Peter, additional, Grevelding, Christoph G., additional, Roeb, Elke, additional, and Roderfeld, Martin, additional

Published
2023
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16. The Humanised NPY-mRFP RBL Reporter Cell Line Is a Fast and Inexpensive Tool for Detection of Allergen-Specific IgE in Human Sera

Author

Prakash, Prema S., primary, Barwary, Nafal J. S., additional, Weber, Michael H. W., additional, Wan, Daniel, additional, Conejeros, Iván, additional, Pereira Moreira, Bernardo, additional, Alharbi, Waleed S., additional, van Hellemond, Jaap J., additional, Akinwale, Jude, additional, and Falcone, Franco H., additional

Published
2022
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19. Are humanized IgE reporter systems potential game changers in serological diagnosis of human parasitic infection?

Author

Prakash, Prema S., Weber, Michael H.W., van Hellemond, Jaap J., Falcone, Franco H., Prakash, Prema S., Weber, Michael H.W., van Hellemond, Jaap J., and Falcone, Franco H.

Abstract

Immunoglobulin E (IgE) is thought to have evolved to protect mammalian hosts against parasitic infections or toxins and plays a central role in the pathogenesis, diagnosis, and therapy of IgE-mediated allergy. Despite the prominence of IgE responses in most parasitic infections, and in stark contrast to its use in the diagnosis of allergy, this isotype is almost completely unexploited for parasite diagnosis. Here, we discuss the perceived or real limitations of IgE-based diagnosis in parasitology and suggest that the recent creation of a new generation of very sensitive cellular IgE-based reporters may represent a powerful new diagnostic platform, but needs to be based on a very careful choice of diagnostic allergens.

Published
2022

25. Quantity and Quality of Basophil RNA Depend on the RNA Extraction Technique

Author

Gibbs, Bernhard F., Falcone, Franco H., Bechmann, Victor G, Hansen, Anette Teo, Poulsen, Lars K, Jensen, Bettina M, Gibbs, Bernhard F., Falcone, Franco H., Bechmann, Victor G, Hansen, Anette Teo, Poulsen, Lars K, and Jensen, Bettina M

Abstract

Basophils have been suggested to express low quantities of RNA, challenging the study of gene expression within these cells. However, the purification technique employed might have an impact on the quantity and quality of RNA purified from basophils. This chapter describes a method which gives an optimal RNA output using a TRIzol-based method in contrast to a commercial kit.

Published
2020

28. The Schistosoma mansoni cyclophilin A epitope 107-121 induces a protective immune response against schistosomiasis

Author

de Melo, Tatiane Teixeira, Mendes, Mariana Moreira, Alves, Clarice Carvalho, Fernandes, Viviane Cristina, Pimenta, Deborah Laranjeira Ferreira, Gai, Fatou, Kalli, Marina, Coelho, Aline, de Azambuja Ribeiro, Rosy Iara Maciel, Falcone, Franco H., Pereira, Rosiane Aparecida da Silva, and Fonseca, Cristina Toscano

Subjects
Global Research Theme - Health and Wellbeing, Immunology, Bio/Medical/Health - Other/Miscellaneous, Molecular Biology
Abstract

Great efforts have been made to identify promising antigens and vaccine formulations against schistosomiasis. Among the previously described Schistosoma vaccine candidates, cyclophilins comprise an interesting antigen that could be used for vaccine formulations. Cyclophilin A is the target for the cyclosporine A, a drug with schistosomicide activity, and its orthologue from Schistosoma japonicum induces a protective immune response in mice. Although Schistosoma mansoni cyclophilin A also represents a promising target for anti-schistosome vaccines, its potential to induce protection has not been evaluated. In this study, we characterized the cyclophilin A (SmCyp), initially described as Smp17.7, analyzed its allergenic potential using in vitro functional assays, and evaluated its ability to induce protection in mice when administered as an antigen using different vaccine formulations and strategies. Results indicated that SmCyp could be successfully expressed by mammalian cells and bacteria. The recombinant protein did not promote IgE-reporter system activation in vitro, demonstrating its probable safety for use in vaccine formulations. T and B-cell epitopes were predicted in the SmCyp sequence, with two of them located within the active isomerase site. The most immunogenic antigen, SmCyp (107–121), was then used for immunization protocols. Immunization with the SmCyp gene or protein failed to reduce parasite burden but induced an immune response that modulated the granuloma area. In contrast, immunization with the synthetic peptide SmCyp (107–121) significantly reduced worm burden (48–50%) in comparison to control group, but did not regulate liver pathology. Moreover, the protection observed in mice immunized with the synthetic peptide was associated with the significant production of antibodies against the SmCyp (107–121) epitope. Therefore, in this study, we identified an epitope within the SmCyp sequence that induces a protective immune response against the parasite, thus representing a promising antigen that could be used for vaccine formulation against schistosomiasis.

Published
2019

30. Screening natural libraries of human milk oligosaccharides against lectins using CaR-ESI-MS

Author

El-Hawiet, Amr, Chen, Yajie, Shams-Ud-Doha, Km, Kitova, Elena N., Kitov, Pavel I., Bode, Lars, Hage, Naim, Falcone, Franco H., and Klassen, John S.

Subjects
health care economics and organizations
Abstract

© 2018 The Royal Society of Chemistry. Human milk oligosaccharides (HMOs) afford many health benefits to breast-fed infants, such as protection against infection and regulation of the immune system, through the formation of non-covalent interactions with protein receptors. However, the molecular details of these interactions are poorly understood. Here, we describe the application of catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) for screening natural libraries of HMOs against lectins. The HMOs in the libraries were first identified based on molecular weights (MWs), ion mobility separation arrival times (IMS-ATs) and collision-induced dissociation (CID) fingerprints of their deprotonated anions. The libraries were then screened against lectins and the ligands identified from the MWs, IMS-ATs and CID fingerprints of HMOs released from the lectin in the gas phase. To demonstrate the assay, four fractions, extracted from pooled human milk and containing ≥35 different HMOs, were screened against a C-terminal fragment of human galectin-3 (hGal-3C), for which the HMOs specificities have been previously investigated, and a fragment of the blood group antigen-binding adhesin (BabA) from Helicobacter pylori, for which the HMO specificities have not been previously established. The structures of twenty-one ligands, corresponding to both neutral and acidic HMOs, of hGal-3C were identified; all twenty-one were previously shown to be ligands for this lectin. The presence of HMO ligands at six other MWs was also ascertained. Application of the assay to BabA revealed nineteen specific HMO structures that are recognized by the protein and HMO ligands at two other MWs. Notably, it was found that BabA exhibits broad specificity for HMOs, and recognizes both neutral HMOs, including non-fucosylated ones, and acidic HMOs. The results of competitive binding experiments indicate that HMOs can interact with BabA at previously unknown binding sites. The affinities of eight purified HMOs for BabA were measured by ESI-MS and found to be in the 103 M-1 to 104 M-1 range.

Published
2018

38. IPSE, a parasite-derived host immunomodulatory protein, is a potential therapeutic for hemorrhagic cystitis.

Author

Zee, Rebecca S., Mbanefo, Evaristus C., Le, Loc H., Pennington, Luke F., Odegaard, Justin I., Jardetzky, Theodore S., Alouffi, Abdulaziz, Akinwale, Jude, Falcone, Franco H., and Hsieh, Michael H.

Subjects
NUCLEAR factor of activated T-cells, CYSTITIS, SCHISTOSOMA mansoni, URINATION disorders
Abstract

Chemotherapy-induced hemorrhagic cystitis is characterized by bladder pain and voiding dysfunction caused by hemorrhage and inflammation. Novel therapeutic options to treat hemorrhagic cystitis are needed. We previously reported that systemic administration of the Schistosomiasis hematobium-derived protein H-IPSEH06 (IL-4-inducing principle from Schistosoma mansoni eggs) is superior to three doses of MESNA in alleviating hemorrhagic cystitis (Mbanefo EC, Le L, Pennington LF, Odegaard JI, Jardetzky TS, Alouffi A, Falcone FH, Hsieh MH. FASEB J 32: 4408-4419, 2018). Based on prior reports by others on S. mansoni IPSE (M-IPSE) and additional work by our group, we reasoned that H-IPSE mediates its effects on hemorrhagic cystitis by binding IgE on basophils and inducing IL-4 expression, promoting urothelial proliferation, and translocating to the nucleus to modulate expression of genes implicated in relieving bladder dysfunction. We speculated that local bladder injection of the S. hematobium IPSE ortholog IPSEH03, hereafter called H-IPSEH03, might be more efficacious in preventing hemorrhagic cystitis compared with systemic administration of IPSEH06. We report that H-IPSEH03, like M-IPSE and H-IPSEH06, activates IgE-bearing basophils in a nuclear factor of activated T-cells reporter assay, indicating activation of the cytokine pathway. Furthermore, H-IPSEH03 attenuates ifosfamide-induced increases in bladder wet weight in an IL-4-dependent fashion. H-IPSEH03 relieves hemorrhagic cystitis-associated allodynia and modulates voiding patterns in mice. Finally, H-IPSEH03 drives increased urothelial cell proliferation, suggesting that IPSE induces bladder repair mechanisms. Taken together, H-IPSEH03 may be a potential novel therapeutic to treat hemorrhagic cystitis by basophil activation, attenuation of allodynia, and promotion of urothelial cell proliferation. [ABSTRACT FROM AUTHOR]

Published
2019
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39. Myeloid-Derived microRNAs, miR-223, miR27a, and miR-652, Are Dominant Players in Myeloid Regulation

Author

Gilicze, Anna B., Wiener, Zoltán, Tóth, Sára, Buzás, Edit, Pállinger, Éva, Falcone, Franco H., and Falus, András

Subjects
Article Subject, hemic and lymphatic diseases
Abstract

In the past few years expanding knowledge has been accumulated about the role of microRNAs (miRNAs) not only in hematopoiesis and cancer, but also in inflammatory and infectious diseases. Regarding myeloid cells, our knowledge is relatively insufficient, therefore we intended to collect the available data of miRNA profiles of myeloid cells. In addition to a rather general myeloid regulator miR-223, two other miRNAs seem to be useful subjects in understanding of myeloid miRNA biology: miR-27a and miR-652. We review functions of these three miRNAs and other myeloid miRNAs focusing on their roles in monocytes, neutrophils, eosinophils, basophils and mast cells.

Published
2014
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43. Basophil stimulation and signaling pathways

Author

Gibbs, Bernhard F, Falcone, Franco H., Knol, Edward F., Gibbs, Bernhard F., Gibbs, Bernhard F, Falcone, Franco H., Knol, Edward F., and Gibbs, Bernhard F.

Abstract

Despite growing use of flow cytometry to analyze the functional characteristics of primary basophils the intracellular signaling cascades that control their ability to elaborate various inflammatory mediators and cytokines remain comparatively obscure. Additionally, some studies require the analysis of pro-allergic and inflammatory mediators, such as histamine, LTC4, and various basophil-derived cytokines (e.g., IL-4 and IL-13). Elucidation of intracellular signaling proteins by Western blotting, cytosolic free calcium concentration by spectrofluorophotometry, and detection of mediator releases, as well as analysis of gene expressions by RT-PCR, generally require relatively large numbers of purified basophils. In selected assays, flow cytometry can enable the analysis of relatively low cell numbers and purity for the expression of intracellular signaling proteins or measurement of cytosolic free calcium concentrations by basophil-specific gating strategies. Unfortunately, many aspects of signal transduction relevant to human basophils cannot be readily extrapolated from the use of basophil or mast cell lines. This chapter therefore focuses on how to employ primary human basophils for studying mediator releases and signaling characteristics.

Published
2014

44. Basophils and Mast Cells

Author

Gibbs, Bernhard F., Falcone, Franco H., Gibbs, Bernhard F, Gibbs, Bernhard F., Falcone, Franco H., and Gibbs, Bernhard F

Published
2014

46. Use of Humanised Rat Basophilic Leukaemia Cell Line RS-ATL8 for the Assessment of Allergenicity of Schistosoma mansoni Proteins

Author

Wan, Daniel, primary, Ludolf, Fernanda, additional, Alanine, Daniel G. W., additional, Stretton, Owen, additional, Ali Ali, Eman, additional, Al-Barwary, Nafal, additional, Wang, Xiaowei, additional, Doenhoff, Michael J., additional, Mari, Adriano, additional, Fitzsimmons, Colin M., additional, Dunne, David W., additional, Nakamura, Ryosuke, additional, Oliveira, Guilherme C., additional, Alcocer, Marcos J. C., additional, and Falcone, Franco H., additional

Published
2014
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48. Serological Screening of the Schistosoma mansoni Adult Worm Proteome

Author

Ludolf, Fernanda, primary, Patrocínio, Paola R., additional, Corrêa-Oliveira, Rodrigo, additional, Gazzinelli, Andréa, additional, Falcone, Franco H., additional, Teixeira-Ferreira, André, additional, Perales, Jonas, additional, Oliveira, Guilherme C., additional, and Silva-Pereira, Rosiane A., additional

Published
2014
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49. Anti-Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) differentially regulate apoptosis in normal and neoplastic human basophils.

Author

Förster, Anja, Falcone, Franco H., Gibbs, Bernhard F., Preussner, Liane M., Fiebig, Britta S., Altunok, Hülya, Seeger, Jens M., Cerny-Reiterer, Sabine, Rabenhorst, Anja, Papenfuss, Kerstin, Valent, Peter, Kashkar, Hamid, Hartmann, Karin, Förster, Anja, Falcone, Franco H., Gibbs, Bernhard F., Preussner, Liane M., Fiebig, Britta S., Altunok, Hülya, Seeger, Jens M., Cerny-Reiterer, Sabine, Rabenhorst, Anja, Papenfuss, Kerstin, Valent, Peter, Kashkar, Hamid, and Hartmann, Karin

Abstract

Basophilia is associated with allergic and parasitic diseases and advanced chronic myeloid leukemia. In the present study, we characterized the expression and function of the death receptors Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors in basophils from healthy donors compared to neoplastic basophils. Peripheral blood basophils obtained from healthy donors (HD-PBB) and from patients with chronic myeloid leukemia (CML-PBB) were found to express high levels of Fas/CD95 and low levels of TRAIL-R2, whereas the basophil-like chronic myeloid leukemia cell line KU-812 expressed significant levels of TRAIL-R1 and TRAIL-R2. HD-PBB underwent apoptosis in response to anti-Fas/CD95, but showed resistance to TRAIL, unless they were co-treated with actinomycin D. Interestingly, CML-PBB and KU-812 cells exhibited the opposite response pattern with resistance to anti-Fas/CD95, but significant susceptibility to TRAIL-induced apoptosis. Our data show that anti-Fas/CD95 and TRAIL differentially regulate apoptosis of normal and neoplastic human basophils, which may direct the development of novel therapeutic strategies.

Published
2013

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