Both Free-Living and Parasitic Nematodes Induce a Characteristic Th2 Response That Is Dependent on the Presence of Intact Glycans

Tawill, S.A.; Goff, Laëtitia Le; Ali, Fahimeda; Blaxter, Mark; Allen, Judith E.

doi:10.1128/iai.72.1.398-407.2004

Cited by 116 publications

(118 citation statements)

References 54 publications

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“…On the other hand, the H. contortus H11 glycoprotein, which also confers protection, is known to be core ␣1,3-fucosylated (46). Furthermore, glycans of parasitic nematodes generate Th2 responses, a fact that also has been found to hold for C. elegans glycans (even though this is not of direct pathogenic significance, because C. elegans is not an animal parasite); and even more significant is preliminary data indicating that fucosylated C. elegans glycans are responsible for the observed Th2 response (60). Therefore, C. elegans fucosylation mutants should be interesting models, not just for biosynthetic and glycomics studies but also for future immunological investigations.…”

Section: Discussionmentioning

confidence: 99%

Molecular Basis of Anti-horseradish Peroxidase Staining in Caenorhabditis elegans

Paschinger

Rendić

Lochnit

et al. 2004

Journal of Biological Chemistry

100

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Cross-reactivity with anti-horseradish peroxidase antiserum is a feature of many glycoproteins from plants and invertebrates; indeed staining with this reagent has been used to track neurons in Drosophila melanogaster and Caenorhabditis elegans. Although in insects the evidence indicates that the cross-reaction results from the presence of core ␣1,3-fucosylated N-glycans, the molecular basis for anti-horseradish peroxidase staining in nematodes has been unresolved to date. By using Western blots of wild-type and mutant C. elegans extracts in conjunction with specific inhibitors, we show that the cross-reaction is due to core ␣1,3-fucosylation. Of the various mutants examined, one with a deletion of the fut-1 (K08F8.3) gene showed no reaction to anti-horseradish peroxidase; the molecular phenotype was rescued by injection of either the K08F8 cosmid or the fut-1 open reading frame under control of the let-858 promoter. Furthermore, expression of fut-1 cDNA in Pichia and insect cells in conjunction with antibody staining, high pressure liquid chromatography, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry analyses showed that FUT-1 is a core ␣1,3-fucosyltransferase with an unusual substrate specificity. It is the only core fucosyltransferase in plants and animals described to date that does not require the prior action of N-acetylglucosaminyltransferase I.

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Section: Discussionmentioning

confidence: 99%

Molecular Basis of Anti-horseradish Peroxidase Staining in Caenorhabditis elegans

Paschinger

Rendić

Lochnit

et al. 2004

Journal of Biological Chemistry

100

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“…For instance, SEA, which contains glycoproteins, is recognized and internalized by human DC in a DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN)-, mannose receptor-and macrophage galactose-type lectin-dependent manner [16,17] [20], suggests that CLR play an important role in conditioning DC for induction of Th2 responses by schistosomal antigens. Moreover, antigens from Toxocara canis were found to be recognized by DC-SIGN expressed on DC [21], and the induction of a Th2 response in vivo by antigens of the parasitic nematode Brugia malayi, as well as the free-living nematode Caenorhabditis elegans, was found to be dependent on intact glycans [22]. These findings together suggest that certain helminth glycans may serve as PAMP that instruct DC via CLR to drive Th2-polarized responses.…”

Section: Introductionmentioning

confidence: 87%

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

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The classical reaction of the host to helminth infections is the induction of Th2 immune responses with a regulatory component. DC, as central players in the induction and maintenance of immune responses, play a prominent role in both these processes, and in recent years considerable progress has been made in elucidating the mechanisms behind the interplay between DC and helminths. It is becoming increasingly clear that helminths modulate DC function not only via direct interactions but also indirectly via host-derived cues. Furthermore, while studies have until recently focused on receptor signalingmediated DC modulation by helminths, evidence is emerging that DC may also respond to helminth infections by sensing stress signals or tissue damage inflicted by the worms or their products. Here, we will discuss these new insights and will link them to the origin and importance of Th2 and regulatory immune responses with respect to the survival of both parasite and host.Key words: DC . Helminth . Th cell polarization . Tissue damage IntroductionThe classical reaction of the host to helminth infections is the induction of Th2 responses. The induction of Th2 immunity has been shown to be important for resistance to helminth infections in various model systems; however, despite induction of a Th2 response, total clearance of the parasites rarely occurs in man (reviewed in [1,2]). This implies that helminths have evolved strategies, such as evasion or suppression of the host immune response that prevent their expulsion and permit their long-term survival. The immune modulatory effects are thought to arise from the helminth's capacity to exploit the host's own system of immune regulation, which is normally crucial for the maintenance of immune homeostasis and self tolerance. In this respect, the induction of Treg has been shown to be one of the most common mechanisms that restrains immune responses against the parasite while also preventing excessive inflammation and tissue damage inflicted by the worms (reviewed in [2,3]). Therefore, it is not surprising that among the variety of mechanisms developed by helminths to influence host immune responses, modulation of DC as pivotal players in the initiation and polarization of adaptive immune responses, including Treg modulation, may have a particularly important role (reviewed in [2,4,5] ) carbohydrate epitope found in schistosoma soluble egg antigens (SEA), has been implicated in TLR4-dependent priming of Th2 responses via DC [9]. However, SEA is also known to be capable of modulating DC for Th2 priming in the absence of TLR signaling [10]. Furthermore, phosphatidylserine (PS) lipids derived from schistosomes and ascaris worms, which carry TLR2-activating molecules, have been shown to promote Th2 responses via DC, but this is not TLR2 dependent [11], whereas monoacetylated PS lipids from schistosomes were found to specifically instruct DC to preferentially induce IL-10-producing Treg in a TLR2-dependent fashion [12]. Although TLR2 does not seem to be essential for Th2 polar...

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“…It is speculated that the inability of recombinant H11 expressed in baculovirus to induce protection may be due to inappropriate glycosylation (Newton and Meeusen, 2003). Interestingly, initial studies suggest that nematode fucosylated glycans may be involved in inducing Th2 responses in mice (Tawill et al, 2004). Analysis of the C. elegans glycome is progressing (Haslam and Dell, 2003;Hanneman et al, 2006) together with identification and functional analysis of many of the enzymes involved in glycosylation (Schachter, 2004).…”

Section: Discussionmentioning

confidence: 99%

Expression and purification of an active cysteine protease of Haemonchus contortus using Caenorhabditis elegans

Murray

Geldhof

Clark

et al. 2007

International Journal for Parasitology

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Many proteolytic enzymes of parasitic nematodes have been identified as possible targets of control. Testing these as vaccine or drug targets is often difficult due to the problems of expressing proteases in a correctly folded, active form in standard expression systems. In an effort to overcome these difficulties we have tested Caenorhabditis elegans as an expression system for a Haemonchus contortus cathepsin L cysteine protease, Hc-CPL-1. Recombinant Hc-CPL-1 with a polyhistidine tag added to the C-terminal was expressed in an active and glycosylated form in C. elegans. Optimal expression was obtained expressing Hc-cpl-1 under control of the promoter of the homologous C. elegans cpl-1 gene. The recombinant protein was purified from liquid cultures by nickel chelation chromatography in sufficient amounts for vaccination studies to be carried out. This study provides proof of principle that active, post-translationally modified parasitic nematode proteases can be expressed in C. elegans and this approach can be extended for expression of known protective antigens. Ó

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Both Free-Living and Parasitic Nematodes Induce a Characteristic Th2 Response That Is Dependent on the Presence of Intact Glycans

Cited by 116 publications

References 54 publications

Molecular Basis of Anti-horseradish Peroxidase Staining in Caenorhabditis elegans

Molecular Basis of Anti-horseradish Peroxidase Staining in Caenorhabditis elegans

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

Expression and purification of an active cysteine protease of Haemonchus contortus using Caenorhabditis elegans

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