Glycan microarray analysis of the carbohydrate-recognition specificity of native and recombinant forms of the lectin ArtinM

Liu, Y.; Cecílio, Nerry T.; Carvalho, Fernanda C.; Roque-Barreira, Maria Cristina; Feizi, Ten

doi:10.1016/j.dib.2015.11.014

Cited by 12 publications

(11 citation statements)

References 5 publications

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“…Although ArtinM recognizes primarily Manα1-3(Manα1-6)Man, which is the common core of N-glycans, the fine specificity of its binding is further determined by a secondary subsite of recognition. It interacts with other carbohydrate residues (Fuc and GlucNAc), which may be contained in the N-glycan, resulting in the particular binding property exhibited by this lectin 32 , 33 , 54 .…”

Section: Discussionmentioning

confidence: 99%

“…This activity was attributed to ArtinM interaction with TLR2 N-glycans 31 , which is followed by IL-12 production and establishment of Th1 immunity. The ArtinM effects were shown to depend on carbohydrate recognition because direct binding to TLR2 was inhibited by the trimannoside specifically targeted by ArtinM 32 , 33 , which constitutes the core of N-glycans. These data demonstrated that a carbohydrate recognition protein might function as a TLR agonist and exert immunomodulatory activity.…”

Section: Introductionmentioning

confidence: 99%

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CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition

Silva¹,

Zorzetto-Fernandes²,

Cecílio³

et al. 2017

Sci Rep

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Agonist interaction with Toll-like receptors (TLRs) induces T cell-mediated immunity, which is effective against intracellular pathogens. Consequently, TLR agonists are being tried as immunomodulatory agents. The lectin ArtinM targets TLR2 N-glycans on macrophages, induces cytokines production, and promotes T helper-1 immunity, a process that culminates in resistance to several parasitic and fungal infections in vivo. Because co-receptors influence agonist binding to TLRs, we investigated whether CD14 is required for macrophage activation induced by ArtinM. Macrophages from wild-type mice stimulated by ArtinM not only produced cytokines but also had the following activation profile: (i) expression of M1 polarization markers; (ii) nitrite oxide production; (iii) cellular migration; (iv) enhanced phagocytic and fungicide activity; (v) modulation of TLR2 expression; and (vi) activation of NF-κB pathway. This activation profile induced by ArtinM was evaluated in macrophages lacking CD14 that showed none of the ArtinM effects. We demonstrated by immunoprecipitation and sugar inhibition assays the physical interaction of ArtinM, TLR2, and CD14, which depends on recognition of the trimannoside that constitutes the core of N-glycans. Thus, our study showed that CD14 is critical for ArtinM-induced macrophage activation, providing fundamental insight into the design of anti-infective therapies based on carbohydrate recognition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition

Silva¹,

Zorzetto-Fernandes²,

Cecílio³

et al. 2017

Sci Rep

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“…This research confirmed the preference of the ArtinM primary site for probes having the core structure Manα1–3[Manα1–6]Manβ1–4. It also showed the contribution of the secondary site of ArtinM to enhancing the affinity of the CRD for probes containing Fucα1–6 or GlcNAcα1–2 associated with Manα1–3[Manα1–6]Manβ1–4 [ 47 , 48 , 49 ]. The core structure Manα1–3[Manα1–6]Manβ1–4 recognized by ArtinM is also targeted by Morniga M [ 50 , 51 ], which is consistent with the marked correlation between the glycan-binding specificities and phylogenies of ArtinM and Morniga M [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells

Silva

Oliveira-Brito

Gonçalves

et al. 2017

IJMS

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The recognition of cell surface glycans by lectins may be critical for the innate and adaptive immune responses. ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus, activates antigen-presenting cells by recognizing TLR2 N-glycans and induces Th1 immunity. We recently demonstrated that ArtinM stimulated CD4+ T cells to produce proinflammatory cytokines. Here, we further studied the effects of ArtinM on adaptive immune cells. We showed that ArtinM activates murine CD4+ and CD8+ T cells, augmenting their positivity for CD25, CD69, and CD95 and showed higher interleukin (IL)-2 and interferon (IFN)-γ production. The CD4+ T cells exhibited increased T-bet expression in response to ArtinM, and IL-2 production by CD4+ and CD8+ T cells depended on the recognition of CD3εγ-chain glycans by ArtinM. The ArtinM effect on aberrantly-glycosylated neoplastic lymphocytes was studied in Jurkat T cells, in which ArtinM induced IL-2, IFN-γ, and IL-1β production, but decreased cell viability and growth. A higher frequency of AnnexinV- and propidium iodide-stained cells demonstrated the induction of Jurkat T cells apoptosis by ArtinM, and this apoptotic response was reduced by caspases and protein tyrosine kinase inhibitors. The ArtinM effects on murine T cells corroborated with the immunomodulatory property of lectin, whereas the promotion of Jurkat T cells apoptosis may reflect a potential applicability of ArtinM in novel strategies for treating lymphocytic leukemia.

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“…The immunomodulatory properties of plant lectins have encouraged their screening for potential pharmaceutical applications, among them, the development of adjuvants. An important characteristic of certain plant lectins rely on their ability to interact with the mucosal epithelium and to be translocated across the gut, which may be exploited in vaccine formulations to induce mucosal and systemic immunity (47, 86) In the last few years, lectins from the jackfruit ( Artocarpus integrifolia ), ArtinM and Jacalin (JAC) have arisen as potential adjuvants in vaccines against protozoan parasites (80, 81, 116–119). In particular, ArtinM, stimulates macrophages and dendritic cells to produce IL-12 (120), through ArtinM interaction with the N-glycans of TLR2 (121), inducing a biased Th1-immune response.…”

Section: Adjuvants: the Black Box Of Immunology Being Openedmentioning

confidence: 99%

Promising Plant-Derived Adjuvants in the Development of Coccidial Vaccines

2019

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Coccidial parasites cause medical and veterinary diseases worldwide, frequently leading to severe illness and important economic losses. At present, drugs, chemotherapeutics and prophylactic vaccines are still missing for most of the coccidial infections. Moreover, the development and administration of drugs and chemotherapeutics against these diseases would not be adequate in livestock, since they may generate unacceptable residues in milk and meat that would avoid their commercialization. In this scenario, prophylactic vaccines emerge as the most suitable approach. Subunit vaccines have proven to be biologically safe and economically viable, allowing researchers to choose among the best antigens against each pathogen. However, they are generally poorly immunogenic and require the addition of adjuvant compounds to the vaccine formulation. During the last decades, research involving plant immunomodulatory compounds has become an important field of study based on their potential pharmaceutical applications. Some plant molecules such as saponins, polysaccharides, lectins and heat shock proteins are being explored as candidates for adjuvant/carriers formulations. Moreover, plant-derived immune stimulatory compounds open the possibility to attain the main goal in adjuvant research: a safe and non-toxic adjuvant capable of strongly boosting and directing immune responses that could be incorporated into different vaccine formulations, including mucosal vaccines. Here, we review the immunomodulatory properties of several plant molecules and discuss their application and future perspective as adjuvants in the development of vaccines against coccidial infections.

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Glycan microarray analysis of the carbohydrate-recognition specificity of native and recombinant forms of the lectin ArtinM

Cited by 12 publications

References 5 publications

CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition

CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition

ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells

Promising Plant-Derived Adjuvants in the Development of Coccidial Vaccines

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