Cutting Edge: IPSE/alpha-1, a Glycoprotein from<i>Schistosoma mansoni</i>Eggs, Induces IgE-Dependent, Antigen-Independent IL-4 Production by Murine Basophils In Vivo

Schramm, Gabriele; Mohrs, Katja; Wodrich, Maren; Doenhoff, Michael J.; Pearce, Edward J.; Haas, Helmut; Mohrs, Markus

doi:10.4049/jimmunol.178.10.6023

Cited by 152 publications

(146 citation statements)

References 26 publications

(43 reference statements)

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“…Branch lengths represent the numbers of amino acid substitutions per site in aligned postions. npg l e t t e r s in basophils and is probably related to immune modulation or alteration in the host, as has been proposed for S. mansoni 20 . Having explored transcription, we then constructed an interaction network for all genes inferred to be essential and transcribed constitutively or in a developmentally regulated manner in S. haematobium.…”

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confidence: 76%

Whole-genome sequence of Schistosoma haematobium

et al. 2012

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Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide 1 . No vaccines are available, and treatment relies on one drug, praziquantel 2 . Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer 1,3 and as a predisposing factor for HIV/AIDS 4,5 . The parasite is transmitted to humans from freshwater snails 1 . Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease 6 and induce squamous cell carcinoma 7 . Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites 8,9 . We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.

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confidence: 76%

Whole-genome sequence of Schistosoma haematobium

et al. 2012

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“…However, since certain allergen and helminth antigens may directly crosslink FcεRI on basophils without the need for specific IgE [34][35][36], these responses may also be enhanced by the presence of TLR ligands at the same time, and TLR activation of basophils may thus contribute to enhanced cytokine production in primary immune responses against helminths as well.…”

Section: Discussionmentioning

confidence: 99%

Activation of human basophils by combined toll‐like receptor‐ and FcεRI‐triggering can promote Th2 skewing of naive T helper cells

et al. 2013

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Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionBasophils are circulating granulocytes that can migrate to tissues when inflammation or other triggers are present locally. Activation of basophils through crosslinking of FcεRI via antigen-specific IgE causes the release of granule contents (histamine, proteoglycans), lipid-derived mediators (leukotrienes), and cytokines. Due to their potent activation via IgE-bound antigens and their production of T helper 2 (Th2) type cytokines such as IL-4 and IL-13, Correspondence: Jolien Suurmond e-mail: j.suurmond@lumc.nl basophils are often considered important innate effector cells in IgE-mediated immune responses. Besides activation through IgE, several other pathways have been described to activate basophils, including activation through complement receptors and toll-like receptors (TLR). Although information about TLR protein expression and the response of basophils to TLR ligands is scarce, human basophils express mRNA of several TLRs, and protein of TLR-2 and -4. However, the functional response of basophils to ligation of most TLRs is unknown [1][2][3][4].Basophil responses to TLR ligands may be important, as it is not understood how pathogens and allergens may lead to induction of Th2 responses. As TLR ligation of dendritic cells most often induces type 1 responses through production of IL-12, it is not understood whether and how Th2 cells can be induced via TLR. Since basophils are a known early source of IL-4 and other cytokines associated with Th2 responses, they have been proposed to play a prominent role in the induction of such responses [8]. In mice, it was suggested that basophils play a crucial role in responses against Th2-associated helminth parasites and in protease allergens [9][10][11]. Basophils were proposed to function as APCs in these studies and were also shown to be present in LNs in models of allergy and helminth infection [12][13][14]. However, the function of basophils as APCs during the priming phase of Th2 responses in mice has been challenged by others [13,15,16], and human basophils could not present antigens to CD4 + T cells [17,18]. Therefore, it seems unlikely that human basophils function as APCs. However, by providing an early IL-4 signal that facilitates Th2 skewing after T-cell activation by APCs, basophils could play an important role in skewing of Th2 responses as accessory cells. Indeed, in a mouse model for papain-induced Th2 responses, both DCs and basophils were important for Th2 skewing [19].Since several allergens and helminth parasites can activate TLRs [20][21][22], it would be of high importance to know whether human basophils can be activated via TLR triggering, and if so, which cytokines are released. Until now, little information on these aspects is available for human basophils. Furthermore, as allergic responses and helminth infections may induce IgE responses [23], it would be important to know whether these pathways would interact and prom...

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“…We and others have shown indeed that basophils could play indispensable roles in the generation of T H 2 cells in an IL-3-dependent manner in vitro, and acceleration of T H 2 differentiation resulted upon expansion of basophils in vivo by continuous exposure to IL-3 19 or in the absence of the transcription factor interferon regulatory factor-2 (IRF-2) 20 . For initiation of T H 2 responses, IL-3 is of particular interests among those molecularly heterogeneous basophils stimulants because this cytokine can directly induce IL-4 production in resting basophils 20 , while other stimuli, such as FcεRI crosslinkage and the allergen protease papain, seemingly require prior activation of basophils for IL-4 induction [21][22][23] . As mentioned above, however, information is severely limited on the IL-3-triggered signaling pathway for IL-4 production, an important effector function of basophils.…”

Section: Introductionmentioning

confidence: 99%

Fc receptor γ-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils

et al. 2008

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The Fc receptor common γ-chain (FcRγ) is a widely expressed adaptor bearing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. We found here that basophils lacking FcRγ developed normally and proliferated efficiently in response to interleukin 3 (IL-3), but were severely impaired in IL-3-induced IL-4 production and in supporting T helper 2 cell differentiation. Through the transmembrane portion, FcRγ associated constitutively with the common β-chain of the IL-3 receptor and signaled via recruiting the kinase Syk. Retrovirus-mediated complementation revealed the essential role for the ITAM of FcRγ in IL-3 signal transduction. These results uncover a novel mechanism for FcRγ function to 'route' selective cytokine-triggered signals into the ITAM-mediated IL-4 production pathway.Hida et al.

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Cutting Edge: IPSE/alpha-1, a Glycoprotein fromSchistosoma mansoniEggs, Induces IgE-Dependent, Antigen-Independent IL-4 Production by Murine Basophils In Vivo

Cited by 152 publications

References 26 publications

Whole-genome sequence of Schistosoma haematobium

Whole-genome sequence of Schistosoma haematobium

Activation of human basophils by combined toll‐like receptor‐ and FcεRI‐triggering can promote Th2 skewing of naive T helper cells

Fc receptor γ-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils

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