ArtinM, a d-mannose-binding lectin from Artocarpus integrifolia, plays a potent adjuvant and immunostimulatory role in immunization against Neospora caninum

Cardoso, Mariana R.D.; Mota, Caroline Martins; Ribeiro, Dâmaso P.; Santiago, Fernanda Maria; Carvalho, Julianne Vargas de; Araújo, Ester Cristina Borges; Silva, Neide M.; Mineo, Tiago W. P.; Roque-Barreira, Maria Cristina; Silva, Deise A. O.

doi:10.1016/j.vaccine.2011.09.136

Cited by 36 publications

(55 citation statements)

References 41 publications

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“…The administration of ArtinM to mice consistently conferred protection against infections by intracellular pathogens. The Th1-skewed response induced by ArtinM is balanced by the induction of IL-10 production, which prevents exacerbated inflammation [12][13][14][15]. As showed in the present study, the IL-10 inducing property was also demonstrated by y-ArtinM.…”

Section: Discussionsupporting

confidence: 81%

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Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM

Cecílio

Carvalho

Liu

et al. 2016

International Journal of Biological Macromolecules

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Recent advances in glycobiology have revealed the essential role of lectins in deciphering the glycocodes at the cell surface to generate important biological signaling responses. ArtinM, a d-mannose-binding lectin isolated from the seeds of jackfruit (Artocarpus heterophyllus), is composed of 16 kDa subunits that are associated to form a homotetramer. Native ArtinM (n-ArtinM) exerts immunomodulatory and regenerative effects, but the potential pharmaceutical applicability of the lectin is highly limited by the fact that its production is expensive, laborious, and impossible to be scaled up. This led us to characterize a recombinant form of the lectin obtained by expression in Saccharomyces cerevisiae (y-ArtinM). In the present study, we demonstrated that y-ArtinM is similar to n-ArtinM in subunit arrangement, oligomerization and carbohydrate binding specificity. We showed that y-ArtinM can exert n-ArtinM biological activities such as erythrocyte agglutination, stimulation of neutrophil migration and degranulation, mast cell degranulation, and induction of interleukin-12 and interleukin-10 production by macrophages. In summary, the expression of ArtinM in yeast resulted in successful production of an active, recombinant form of ArtinM that is potentially useful for pharmaceutical application.

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Section: Discussionsupporting

confidence: 81%

“…Systemic administration of ArtinM induces Th1 immunity that confers protection against various intracellular pathogens [10,[12][13][14][15]. Topical administration of ArtinM promotes regeneration of injured corneal epithelium and oral mucosa [16,17].…”

Section: Introductionmentioning

confidence: 99%

Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM

Cecílio

Carvalho

Liu

et al. 2016

International Journal of Biological Macromolecules

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“…This ability accounts for the protection conferred by ArtinM against Paracoccidioides brasiliensis , which is dependent on TLR2 [19], [22]. ArtinM also promotes resistance to infection by other intracellular pathogens, such as Leishmania major [20], Leishmania amazonensis [21], Neospora caninum [23], and Candida albicans [24].…”

Section: Introductionmentioning

confidence: 99%

Recognition of TLR2 N-Glycans: Critical Role in ArtinM Immunomodulatory Activity

Mariano¹,

Zorzetto-Fernandes²,

Silva³

et al. 2014

PLoS ONE

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TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL)-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties.

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“…One group was treated with sulfadiazine (250 mg diluted in 400 mL of drinking water given to the animals for 6 days), whereas four groups were treated for 6 days, at 1-day intervals, intraperitoneally, according with the following preparations: 50 μg of ScLL; 50 μg of ScLL plus 1 μg of ArtinM; 1 μg ArtinM; or PBS only. These lectin concentrations were chosen based on previous studies (Cardoso et al, 2011, 2012). Thirty days after infection the surviving animals were euthanized and their brains collected to determine the rates of parasitism burden.…”

Section: Methodsmentioning

confidence: 99%

“…It has been described in the literature that lectins from plants, such as ArtinM from seeds of jackfruit ( Artocarpus integrifolia ) and ScLL from the latex of the Euphorbiaceae Synadenium carinatum , when used as immunological adjuvants in vaccination protocols, can control parasite infections caused by Leishmania major, Leishmania amazonensis or Neospora caninnun (Panunto-Castelo et al, 2001; Teixeira et al, 2006; Afonso-Cardoso et al, 2007; Toledo et al, 2009; Cardoso et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

Lectins from Synadenium carinatum (ScLL) and Artocarpus heterophyllus (ArtinM) Are Able to Induce Beneficial Immunomodulatory Effects in a Murine Model for Treatment of Toxoplasma gondii Infection

Souza

Ramos

Santana

et al. 2016

Front. Cell. Infect. Microbiol.

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Infection by Toxoplasma gondii affects around one-third of world population and the treatment for patients presenting toxoplasmosis clinically manifested disease is mainly based by a combination of sulfadiazine, pyrimethamine, and folinic acid. However, this therapeutic protocol is significantly toxic, causing relevant dose-related bone marrow damage. Thus, it is necessary to improve new approaches to investigate the usefulness of more effective and non-toxic agents for treatment of patients with toxoplasmosis. It has been described that lectins from plants can control parasite infections, when used as immunological adjuvants in vaccination procedures. This type of lectins, such as ArtinM and ScLL is able to induce immunostimulatory activities, including efficient immune response against parasites. The present study aimed to evaluate the potential immunostimulatory effect of ScLL and ArtinM for treatment of T. gondii infection during acute phase, considering that there is no study in the literature accomplishing this issue. For this purpose, bone marrow-derived macrophages (BMDMs) were treated with different concentrations from each lectin to determine the maximum concentration without or with lowest cytotoxic effect. After, it was also measured the cytokine levels produced by these cells when stimulated by the selected concentrations of lectins. We found that ScLL showed high capacity to induce of pro-inflammatory cytokine production, while ArtinM was able to induce especially an anti-inflammatory cytokines production. Furthermore, both lectins were able to increase NO levels. Next, we evaluated the treatment effect of ScLL and ArtinM in C57BL/6 mice infected by ME49 strain from T. gondii. The animals were infected and treated with ScLL, ArtinM, ArtinM plus ScLL, or sulfadiazine, and the following parameters analyzed: Cytokines production, brain parasite burden and survival rates. Our results demonstrated that the ScLL or ScLL plus ArtinM treatment induced production of pro-inflammatory and anti-inflammatory cytokines, showing differential but complementary profiles. Moreover, when compared with non-treated mice, the parasite burden was significantly lower and survival rates higher in mice treated with ScLL or ScLL plus ArtinM, similarly with sulfadiazine treatment. In conclusion, the results demonstrated the suitable potential immunotherapeutic effect of ScLL and ArtinM lectins to control acute toxoplasmosis in this experimental murine model.

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ArtinM, a d-mannose-binding lectin from Artocarpus integrifolia, plays a potent adjuvant and immunostimulatory role in immunization against Neospora caninum

Cited by 36 publications

References 41 publications

Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM

Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM

Recognition of TLR2 N-Glycans: Critical Role in ArtinM Immunomodulatory Activity

Lectins from Synadenium carinatum (ScLL) and Artocarpus heterophyllus (ArtinM) Are Able to Induce Beneficial Immunomodulatory Effects in a Murine Model for Treatment of Toxoplasma gondii Infection

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