Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated

Klaver, Elsenoor J.; Kuijk, Loes M.; Laan, Lisa C.; Kringel, Helene; Vliet, Sandra J. van; Bouma, Gerd; Cummings, Richard D.; Kraal, Georg; Die, Irma van

doi:10.1016/j.ijpara.2012.10.021

Cited by 97 publications

(129 citation statements)

References 72 publications

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“…The presence of worm-derived soluble factors is supported by experiments that use extracts from H. diminuta worms (41) or dead schistosome ova to protect mice from colitis (17). Helminths produce a number of products with immune modulatory properties (7, 44–49). For instance, helminths produce molecules that induce Tregs (7).…”

Section: Mechanisms Of Regulationmentioning

confidence: 99%

Helminth Infections Decrease Host Susceptibility to Immune-Mediated Diseases

Weinstock

Elliott

2014

The Journal of Immunology

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Helminthic infection has become rare in highly industrialized nations. Concurrent with the decline in helminthic infection is an increase in prevalence of inflammatory disease. Removal of helminths from our environment and their powerful effects on host immunity may have contributed to this increase. Several different helminth species can abrogate disease in murine models of inflammatory bowel disease, type 1 diabetes, multiple sclerosis and other conditions. Helminths evoke immune regulatory pathways often involving dendritic cells, Tregs and macrophages that help control disease. Cytokines such as IL4, IL10 and TGFβ have a role. Notable is helminthic modulatory effect on innate immunity, which impedes development of aberrant adaptive immunity. Investigators are identifying key helminth-derived immune modulatory molecules that may have therapeutic utility in the control of inflammatory disease.

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Section: Mechanisms Of Regulationmentioning

confidence: 99%

Helminth Infections Decrease Host Susceptibility to Immune-Mediated Diseases

Weinstock

Elliott

2014

The Journal of Immunology

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“…Recent elegant studies on structural glycomics profiling of schistosomes have shown that schistosome eggs contain a diverse repertoire of high-mannose, truncated, and complex N-glycans with core motifs such as ␣3 fucose, ␣6 fucose, and ␤2 xylose (27)(28)(29)49). There is also growing evidence that worm products have immunomodulatory roles and can alter the functions and activation of dendritic cells, macrophages, and intestinal epithelial cells (73)(74)(75)(76)(77). However, the precise structures of the molecules that are bioactive in that regard are not yet clear.…”

Section: Discussionmentioning

confidence: 99%

Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray

et al. 2016

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f Infection of mammals by the parasitic helminth Schistosoma mansoni induces antibodies to glycan antigens in worms and eggs, but the differential nature of the immune response among infected mammals is poorly understood. To better define these responses, we used a shotgun glycomics approach in which N-glycans from schistosome egg glycoproteins were prepared, derivatized, separated, and used to generate an egg shotgun glycan microarray. This array was interrogated with sera from infected mice, rhesus monkeys, and humans and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which also were analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fuc␣3GalNAc␤4(Fuc␣3)GlcNAc-R], which is also recognized by the IgG monoclonal antibody F2D2. The FLDNF antigen is expressed by all life stages of the parasite in mammalian hosts, and F2D2 can kill schistosomula in vitro in a complement-dependent manner. Different antisera also recognized other glycan determinants, including core ␤-xylose and highly fucosylated glycans. Thus, the natural shotgun glycan microarray of schistosome eggs is useful in identifying antigenic glycans and in developing new anti-glycan reagents that may have diagnostic applications and contribute to developing new vaccines against schistosomiasis. Schistosomiasis is a major health problem in tropical and subtropical areas where it is endemic, with more than 200 million people actively infected and 800 million at risk of contracting the disease (1-3). Current treatment for disease is limited to the drug praziquantel (4), but cases of drug resistance have been reported (5). Decades of research on schistosomiasis vaccines have yielded only two candidates for clinical trials, and no encouraging results have been published yet (6-9). Thus, there is an urgent need to develop more sensitive diagnostic methods and to identify new vaccine candidates.Recent studies have shown that a major part of the host immune response to infection is directed against carbohydrate (glycan) antigens in glycoproteins and glycolipids (10-17). A wide variety of unusual antigenic determinants include glycans containing the LDN, fucosylated LDN sequences (LDNF, LDN-dF, FLDN, and FLDNF), Lewis X (Le x ), poly-Le x , core ␣3 fucose, and core ␤2 xylose structures (Fig. 1) (11, 14, 17), many of which are expressed by all developmental stages of schistosomes (18). Interestingly, monoclonal antibodies (MAbs) specific to these glycans recognize these antigens on the surface of 3-h-old schistosomula, and some anti-glycan antibodies can mediate killing in vitro in a complement-dependent fashion (18-21). Schistosoma mansoniinfected rhesus monkeys, which are known to self-cure after infection, have IgG to many glycan antigens, including Le x , LDN, LDNF, core fucose, and core xylose determinants, and their sera are effective in complement-mediated cytolysis of cells expressing Le x as well as schistosomulum larvae in ...

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“…IL-10 is implicated in the induction of Th2 and regulatory responses [94] and since ES L1 with altered glycan structure do not have the full capacity compared to the native ES L1 to promote the release of this cytokine, it can be concluded that ES L1 glycans are important for the induction of the immune response characteristic for T. spiralis. Several studies have shown that helminth glycans originating from S. mansoni , A. vitae , and T. suis have an important role in defining DCs phenotype and cytokine production [95–97]. The ability of T. spiralis ES L1 to affect T cell proliferation and polarization either through incompletely mature DCs or independently of these cells, both in vitro and in vivo , will be addressed in the following section.…”

Section: Antigen Presenting Cells and T Spiralis Es L1 (Receptorsmentioning

confidence: 99%

Secretory Products ofTrichinella spiralisMuscle Larvae and Immunomodulation: Implication for Autoimmune Diseases, Allergies, and Malignancies

Sofronić-Milosavljević

Ilić

Pinelli

et al. 2015

Journal of Immunology Research

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Trichinella spiralis has the unique ability to make itself “at home” by creating and hiding in a new type of cell in the host body that is the nurse cell. From this immunologically privileged place, the parasite orchestrates a long-lasting molecular cross talk with the host through muscle larvae excretory-secretory products (ES L1). Those products can successfully modulate parasite-specific immune responses as well as responses to unrelated antigens (either self or nonself in origin), providing an anti-inflammatory milieu and maintaining homeostasis. It is clear, based on the findings from animal model studies, that T. spiralis and its products induce an immunomodulatory network (which encompasses Th2- and Treg-type responses) that may allow the host to deal with various hyperimmune-associated disorders as well as tumor growth, although the latter still remains unclear. This review focuses on studies of the molecules released by T. spiralis, their interaction with pattern recognition receptors on antigen presenting cells, and subsequently provoked responses. This paper also addresses the immunomodulatory properties of ES L1 molecules and how the induced immunomodulation influences the course of different experimental inflammatory and malignant diseases.

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Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated

Cited by 97 publications

References 72 publications

Helminth Infections Decrease Host Susceptibility to Immune-Mediated Diseases

Helminth Infections Decrease Host Susceptibility to Immune-Mediated Diseases

Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray

Secretory Products ofTrichinella spiralisMuscle Larvae and Immunomodulation: Implication for Autoimmune Diseases, Allergies, and Malignancies

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