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Review
. 2013 Oct;30(7):641-57.
doi: 10.1007/s10719-012-9464-4. Epub 2013 Jan 9.

The immunomodulatory effect of plant lectins: a review with emphasis on ArtinM properties

Maria A Souza  1 , Fernanda C Carvalho, Luciana P Ruas, Rafael Ricci-Azevedo, Maria Cristina Roque-Barreira
Affiliations
Review

The immunomodulatory effect of plant lectins: a review with emphasis on ArtinM properties

Maria A Souza et al. Glycoconj J. 2013 Oct.

Abstract

Advances in the glycobiology and immunology fields have provided many insights into the role of carbohydrate-protein interactions in the immune system. We aim to present a comprehensive review of the effects that some plant lectins exert as immunomodulatory agents, showing that they are able to positively modify the immune response to certain pathological conditions, such as cancer and infections. The present review comprises four main themes: (1) an overview of plant lectins that exert immunomodulatory effects and the mechanisms accounting for these activities; (2) general characteristics of the immunomodulatory lectin ArtinM from the seeds of Artocarpus heterophyllus; (3) activation of innate immunity cells by ArtinM and consequent induction of Th1 immunity; (4) resistance conferred by ArtinM administration in infections with intracellular pathogens, such as Leishmania (Leishmania) major, Leishmania (Leishmania) amazonensis, and Paracoccidioides brasiliensis. We believe that this review will be a valuable resource for more studies in this relatively neglected area of research, which has the potential to reveal carbohydrate targets for novel prophylactic and therapeutic strategies.

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Figures

Fig. 1
Fig. 1
Three-dimensional structure of the ArtinM monomer. Motifs are distinguished by color, and the positions of the mannose-binding site and linker region are indicated. (Authorized reproduction from Rosa et al. [63])
Fig. 2
Fig. 2
Immunological repercussions of ArtinM binding to antigen-presenting cells (APCs). The interaction of ArtinM with TLR2 N-glycans on APCs promotes IL-12 production. This cytokine induces increased IFN-γ production by natural killer (NK) and/or T cells, shaping a Th1 immune response. IFN-γ increases the microbicidal activity of macrophages. ArtinM stimulation of infected macrophages further increases the release of IL-12, constituting an amplification looping of Th1 immunity against intracellular pathogens
Fig. 3
Fig. 3
ArtinM administration avoids the footpad lesion caused by L. major inoculation in BALB/c mice. Mice were administered with ArtinM (10 μg/mL) or vehicle (PBS) and infected (in the hind footpads) with 1 × 106 metacyclic promastigotes of L. major. The evolution of the lesion was assessed by measuring the footpad thickness, during an 8-week period. Modified of Panunto-Castelo et al. [26]
Fig. 4
Fig. 4
Protective effect of ArtinM against P. brasiliensis infection. Untreated and ArtinM (10 μg/mL) treated BALB/c mice were intravenously infected with 1 × 106 virulent P. brasiliensis yeast cells. At the week 2 postinfection, the pulmonary tissue from untreated mice presented large granulomas surrounding a great number of yeast cells (a), while ArtinM treated mice showed small areas of mononuclear cells infiltration, in which few yeast cells were seen (b)
Fig. 5
Fig. 5
Pleiotropic activity of ArtinM allows the construction of a Th1 immunity regulated by IL-10. ArtinM administration leads to the production of Th1 cytokines and IL-10, whereas no IL-4 is detected. The cell responding to ArtinM stimulus through IL-10 production has not yet been identified. IL-10 is assumed to counterbalance the inflammation associated with Th1 immunity, thereby preventing tissue injury
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