The use of mouse/human chimaeric antibodies to investigate the roles of different antibody isotypes, including lgA2, in the killing of Schistosoma mansoni schistosomula by eosinophils

Dunne, David W.; Richardson, Brian A.; Jones, Frances M.; Clark, Mike; Thorne, Kareen J. I.; Butterworth, Anthony E.

doi:10.1111/j.1365-3024.1993.tb00598.x

Cited by 44 publications

(31 citation statements)

References 21 publications

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“…Like the other FcRs associated to ITAMs, cross-linking of FcaR via Fc fragments of IgA triggers several biological responses which seem to be dependent on the cell type in the myeloid lineage. These responses, which are generally mediated by Ca 2z mobilization and PKC activation [97], include phagocytosis of IgA immune complexes [120,121], antibody-dependent cell-mediated cytotoxicity [120], killing of IgAopsonized bacteria and parasites [122][123][124], and production of reactive oxygen intermediates [64,125,126], inflammatory mediators and cytokines [127], as well as leukotrienes and prostaglandins [128]. Crosslinking of FcaR by IgA complexes on monocytes induces an increased production of TNF-a, IL-1b and IL-6 [99,[128][129][130].…”

Section: Immunoglobulin-a Leukocyte Receptor-mediated Leukocyte Responsementioning

confidence: 99%

“…This is a relevant effect, especially at mucosal surfaces where the inflammatory response and released cytokines following bacterial adherence and/or invasion can stimulate both FcaR expression and phagocytosis of IgAopsonized particles by PMN [131]. FcaR also plays an important role in eosinophil degranulation [132] and killing of parasites such as schistosomes [124]. In addition, eosinophils may also bind SIgA via a specific receptor for SC and therefore constitute potential candidates in host mucosal defence against parasite invasion.…”

Section: Immunoglobulin-a Leukocyte Receptor-mediated Leukocyte Responsementioning

confidence: 99%

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Lung mucosal immunity: immunoglobulin-A revisited

et al. 2001

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Mucosal defence mechanisms are critical in preventing colonization of the respiratory tract by pathogens and penetration of antigens through the epithelial barrier. Recent research has now illustrated the active contribution of the respiratory epithelium to the exclusion of microbes and particles, but also to the control of the inflammatory and immune responses in the airways and in the alveoli. Epithelial cells also mediate the active transport of polymeric immunoglobulin-A from the lamina propria to the airway lumen through the polymeric immunoglobulin receptor. The role of IgA in the defence of mucosal surfaces has now expanded from a limited role of scavenger of exogenous material to a broader protective function with potential applications in immunotherapy. In addition, the recent identification of receptors for IgA on the surface of blood leukocytes and alveolar macrophages provides an additional mechanism of interaction between the cellular and humoral immune systems at the level of the respiratory tract.

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Section: Immunoglobulin-a Leukocyte Receptor-mediated Leukocyte Responsementioning

confidence: 99%

Section: Immunoglobulin-a Leukocyte Receptor-mediated Leukocyte Responsementioning

confidence: 99%

Lung mucosal immunity: immunoglobulin-A revisited

et al. 2001

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“…The cleavage of IgE by schistosomes into a molecule which is unable to engage FcεRII receptors is likely to be an important immune evasion strategy employed by the parasite, and may partially explain why IgA has been observed to be more effective at killing schistosomula than IgE in vitro [41]. The demonstration that IgE cleavage is most likely attributable to the schistosomal elastase will stimulate interest in this enzyme as an important target for therapy.…”

Section: Discussionmentioning

confidence: 99%

Cleavage of Human IgE Mediated by <i>Schistosoma mansoni</i>

Pleass

Kusel²,

Woof³

2000

Int Arch Allergy Immunol

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Background: IgE-mediated mechanisms are important in protection against helminth parasites. However, schistosomes are long-lived in mammalian hosts, presumably as a result of immune evasion strategies. We sought evidence for one such strategy, namely specific cleavage of host IgE. Methods: Human IgE, IgA and IgG were incubated with extracts from cercarial and schistosomular stages of Schistosoma mansoni or with schistosomular culture supernatants. The resulting products were analysed by Western blotting with Ig-specific antibodies. Numerous protease inhibitors were assessed for ability to inhibit the observed cleavage of IgE by the extracts. Partial purification of the IgE-proteolytic activity from cercarial extract was achieved by gel filtration. To test IgE function, we compared the abilities of untreated and schistosomular-treated IgE to mediate rosette formation through interaction with Fcε receptors. Results: Cercarial and schistosomular extracts were found to cleave human, mouse and rat IgE but not human IgA1, IgA2 or IgG1. Schistosomular culture supernatants displayed similar proteolytic activity towards IgE. Immunoblotting suggested that cleavage occurred close to the Cε2/Cε3 domain interface of the IgE heavy chain. PMSF and elastatinal inhibited cleavage, suggesting that the protease involved is an elastase-like serine protease, particularly since porcine pancreatic elastase also cleaved IgE to give similar-sized products. Further, the chloromethyl ketone derivatized peptide MeO-Suc-Ala-Ala-Pro-Leu- CMK, known to specifically inhibit the schistosome elastase, prevented IgE cleavage. Cleavage of human IgE rendered the antibody molecule unable to interact with U937 cells expressing FcεRII. Conclusions: An elastase-like protease in S. mansoni is able to render IgE non-functional.

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“…IgG4 has no cytotoxic activity and can block the effects of IgG1, IgG2, and IgG3 (13). Furthermore, other studies have indicated a role for IgE and IgA in the elimination of schistosomula through similar mechanisms (14,15).…”

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confidence: 92%

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

et al. 2016

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c Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted Nglycans with terminal mannose residues, Gal␤1-4GlcNAc (LacNAc) and Gal␤1-4(Fuc␣1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAc␤1-4(GlcNAc␤1) n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAc␤1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage-and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection. Schistosomiasis is one of the neglected tropical diseases with the highest impacts on human health. Over 230 million people are infected worldwide, and over 500 million are at risk of infection (1-3). Infection leads to chronic disease characterized by pronounced immunological reactions against eggs deposited into host tissues by the adult schistosome worms, which eventually lead to fibrosis and organ failure (2). Although effective treatment is available, reinfection occurs rapidly and immunity develops only slowly, stressing the need for a prophylactic vaccine as part of a sustainable control strategy (4-6).Schistosomes have a complex life cycle with different life stages that interact with the human host and that each play a role in immunology, immunopathology, and maintenance of infection. Schistosoma infection occurs after direct contact with water containing the larval form of the parasite (cercariae). Cercariae penetrate the host skin and transform into schistosomula, which enter the vasculature and mature while migrating via the lungs to the portal ve...

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The use of mouse/human chimaeric antibodies to investigate the roles of different antibody isotypes, including lgA2, in the killing of Schistosoma mansoni schistosomula by eosinophils

Cited by 44 publications

References 21 publications

Lung mucosal immunity: immunoglobulin-A revisited

Lung mucosal immunity: immunoglobulin-A revisited

Cleavage of Human IgE Mediated by <i>Schistosoma mansoni</i>

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

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