The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x

Die, Irma van; Vliet, Sandra J. van; Nyame, A. Kwame; Cummings, Richard D.; Bank, Christine M C; Appelmelk, Ben J.; Geijtenbeek, Teunis B. H.; Kooyk, Yvette van

doi:10.1093/glycob/cwg052

Cited by 284 publications

(208 citation statements)

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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]. Antigen preparations of other stages of the schistosome life cycle have also been shown to interact with DC-SIGN [18].…”

Section: Modulation Of DC Function By Direct Interaction With Helmintmentioning

confidence: 99%

“…Antigen preparations of other stages of the schistosome life cycle have also been shown to interact with DC-SIGN [18]. Binding of SEA to DC-SIGN is dependent on the sugar motifs Le x and LDN-F [17], while chemical modification of the glycans present in SEA abolishes the Th2-driving capacity of SEA [19]. This, together with the observation that Le x -containing LNFPIII favors Th2-biased responses [20], suggests that CLR play an important role in conditioning DC for induction of Th2 responses by schistosomal antigens.…”

Section: Modulation Of DC Function By Direct Interaction With Helmintmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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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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“…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]. Antigen preparations of other stages of the schistosome life cycle have also been shown to interact with DC-SIGN [18].…”

Section: Modulation Of DC Function By Direct Interaction With Helmintmentioning

confidence: 99%

Section: Modulation Of DC Function By Direct Interaction With Helmintmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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“…In addition to HIV, DC-SIGN was recently shown to bind a variety of microorganisms such as CMV [4], Ebola virus [5], Dengue virus [6], hepatitis C virus [7,8], simian immunodeficiency virus [9], Leishmania [10], Candida albicans [11], Mycobacterium [12][13][14] and Schistosoma [15]. Some pathogens subvert DC functions to escape immune surveillance [16].…”

Section: Introductionmentioning

confidence: 99%

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

et al. 2006

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Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN), a specific C-type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC-SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus-like particles (VLP) bind to DC-SIGN expressed on transfected Raji cells and that antibodies against DC-SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/ chemokines. Although our results indicate that DC-SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF-a, IL-6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC-SIGN was blocked by anti-DC-SIGN antibodies. These results suggest that DC-SIGN has a functional role in DC activation induced by HPV-16 L1-VLP, and thus highlight new aspects of DC interactions with HPV VLP. IntroductionThe C-type lectin dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) is a pathogen recognition receptor that interacts with mannose residues of glycoproteins in a calciumdependent manner via its C-terminal carbohydrate recognition domain [1,2]. DC-SIGN acts both as an adhesion molecule and pathogen recognition receptor, facilitating DC binding and internalization of several viruses, including HIV-1 [3].In addition to HIV, DC-SIGN was recently shown to bind a variety of microorganisms such as CMV [4], Ebola virus [5], Dengue virus [6], hepatitis C virus [7,8], simian immunodeficiency virus [9], Leishmania [10], Candida albicans [11], Mycobacterium [12][13][14] and Schistosoma [15]. Some pathogens subvert DC functions to escape immune surveillance [16]. DC-SIGN is abundantly expressed primarily on DC, including those derived from monocytes and those located beneath the genital surface [3].Human papillomavirus (HPV) virus-like particles (VLP) are a promising vaccine candidate for HPV and cervical cancer [17][18][19][20]. Recent clinical trials have shown that VLP afford excellent protection against persistent infection [20,21]. Because of the lack of a suitable cell culture system for in vitro propagation of HPV and the unavailability of virions, HPV VLP have been used as soluble surrogates for native virus particles. The routes of HPV-16 L1-VLP entry in DC and the nature of cellular receptors involved in capture have been studied but remain to be fully characterized. HPV VLP Here, we report that HPV-16 L1-VLP particles bind to DC-SIGN in transfected cell lines, and to a lesser extent in DC, and that this interaction participates in L1-VLPinduced activation of DC. Thus, DC-SIGN is likely involved in DC activation by HPV VLP. Results and discussion HPV L1-VLP bind to DC-SIGN in DC-SIGN-transfected cell linesTo study interactions between L1-VLP and DC-SIGN, we...

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“…Por ejemplo, las microfilarias de Brugia malayi, cuando son capturadas por las CD, inhiben la producción de IL-12 en respuesta a antígenos de Staphylococcus aureus (44). Varios componentes de Schistosoma mansoni actúan directamente sobre las CD, tales como algunos glicanos que son reconocidos a través de CD209 y promueven la polarización hacia Th2 (45). Otro es el lípido fosfatidil-serina, reconocido por el receptor-2 tipo Toll (Toll-like receptor-2) en las DC, que induce el desarrollo de Treg (46).…”

Section: Células No Linfoides De La Respuesta Innataunclassified

Inmunorregulación inducida por helmintos: una actualización

Zakzuk

2016

iatreia

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Las helmintiasis, que han desaparecido o disminuido en las regiones más desarrolladas del mundo, producen cambios notables en el sistema inmunológico, y usualmente, cuando son crónicas o intensas, causan inmunosupresión. Aunque deterioran la salud, también parecen proteger del desarrollo de enfermedades inflamatorias crónicas al proveer estímulos inmunorreguladores. Promueven el desarrollo de linfocitos B o T reguladores que inhiben la proliferación de clones autorreactivos o específicos de alérgeno. Cada vez se conoce más la modulación de la respuesta innata por parásitos; se destaca que además de aumentar en número células claves en la defensa contra estos, también pueden usarlas como blanco de evasión. Algunas poblaciones importantes en la defensa contra bacterias y otros patógenos también responden a los helmintos, pero sufren una programación genética diferente a las formas asociadas a la respuesta tipo 1. Paralelamente a la inmunosupresión, las helmintiasis inducen una respuesta tipo 2. Por esto, es preocupante lo que sucede en algunas poblaciones en donde se controlan parcialmente estas parasitosis y predominan los ciclos de infestación ligera/reinfección. En estos contextos, algunos helmintos, como Ascaris lumbricoides, parecen promover el desarrollo de alergias; esta es la helmintiasis más común en el planeta, pero de la que menos se sabe sobre su capacidad inmunorreguladora. PALABRAS CLAVEAscaris lumbricoides; Helmintiasis; Inmunomodulación; Inmunosupresión SUMMARY Helminth-induced immunoregulation: an updateHelminth infections, which have been reduced or eradicated from most developed countries, produce important changes in the immune system. Especially, when chronic and intense, they 1 MD, PhD. Doctorado en Ciencias Biomédicas.

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The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x

Cited by 284 publications

References 50 publications

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

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

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

Inmunorregulación inducida por helmintos: una actualización

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