Elsevier

Vaccine

Volume 24, Issue 15, 5 April 2006, Pages 3001-3008
Vaccine

Potential of KM+ lectin in immunization against Leishmania amazonensis infection

https://doi.org/10.1016/j.vaccine.2005.11.067Get rights and content

Abstract

In the present study we evaluated Canavalia brasiliensis (ConBr), Pisum arvense (PAA) and Artocarpus integrifolia (KM+) lectins as immunostimulatory molecules in vaccination against Leishmania amazonensis infection. Although they induced IFN-γ production, the combination of the lectins with SLA antigen did not lead to lesion reduction. However, parasite load was largely reduced in mice immunized with KM+ lectin and SLA. KM+ induced a smaller inflammatory reaction in the air pouch model and was able to inhibit differentiation of dendritic cells (BMDC), but to induce maturation by enhancing the expression of MHC II, CD80 and CD86. These observations indicate the modulatory role of plant lectins in leishmaniasis vaccination may be related to their action on the initial innate response.

Introduction

Leishmania parasites are intracellular protozoa that cause a variety of disease that can range from a self-healing cutaneous lesion to a visceral disseminated disease. Cutaneous leishmaniasis is the most common form that can be caused by L. amazonensis and L. braziliensis in South America, including Brazil [1]. In experimental cutaneous leishmaniasis, it has been clear that host protection depends on the expansion of Th1 CD4+T cells and suppression of Th2 CD4+T cells [2], [3], [4], [5], [6]. Lymphocytes committed to a Th1 profile are classically known to secrete mainly IFN-γ, a major macrophage activator factor, in response to IL-12 stimulation. Although, the role of Th1 cells is clear, the mechanisms governing the expansion of Th1 and Th2 cells in vivo are currently unexplained. During these early events, the role of antigen presenting cells (APC) is critical to direct the response to a specific phenotype. Among this cells, dendritic cells (DC) are known as professional APC because of their natural potential to process and present antigens. The early production of some cytokines during this initial step is important to define a Th1 or Th2 response.

Many molecules have been tested in order to drive a protective Th1 response. Lectins are proteins with the capacity to bind specifically to carbohydrates [7]. They have been isolated from many different sources including higher plant seeds, animal tissues and algae. Plant lectins have been described for their immunostimulatory potential to cell proliferation and lymphokine production. Lectin from Canavalia brasiliensis (ConBr) is able to induce IFN-γ production by human lymphocytes [8]. ConBr and the lectin from Pisum arvense (PAA) were able to directly stimulate murine macrophages and lymphocytes both in vitro and in vivo to produce NO. In addition, animals treated with this lectins were able to maintain NO production ex vivo [9]. NO is the major molecule that mediates Leishmania killing and its production is induced by IFN-γ [10]. A lectin from Artocarpus integrifolia (KM+) induced IL-12p40 production by macrophages, which then stimulates IFN-γ production by lymphocytes. Moreover, immunization of BALB/c mice with KM+ lectin and SLA antigen from Leishmania major resulted in protection against further challenge [11].

In the present report we explore the immunostimulatory potential of three plant lectins, Canavalia brasiliensis (ConBr), Pisum arvense (PAA) or Artocarpus integrifolia (KM+) in the immunization against Leishmania. Our results indicate that only mice immunized with KM+ lectin were able to control Leishmania infection probably due to the capacity of KM+ to act on the initial innate response by modifying inflammatory and dendritic cell responses.

Section snippets

Lectins

Lectin from Canavalia ensiformis (ConA) was obtained from Sigma (Sigma/St. Louis, EUA). Lectins from Canavalia brasiliensis (ConBr) and Pisum arvense (PAA) and Artocarpus integrifolia lectin (KM+) were obtained according to methods previously described [12], [13], [14]. The concentrations of the lectins were determined based on previous work [8], [9], [11].

All lectins preparations used were free of bacterial endotoxin.

Mice, parasites and preparation of SLA antigen

Inbred BALB/c of both sexes, 8–12 weeks of age were obtained from the central

Immunization of BALB/c mice with ConBr, PAA or KM+ lectins

BALB/c mice were immunized with SLA (10 μg/ml) in combination or not with ConBr, PAA or KM+ and challenged 15 days after the last booster with Leishmania amazonensis (BA125). The immunization with ConBr or PAA lectins alone or in combination with SLA did not result in lesion size reduction (Fig. 1A and B), while immunization with KM+ lectin alone resulted in significant lesion size reduction (p = 0.0049) when compared to the non-immunized control (Fig. 1C). Since lesion size not always correlates

Discussion

The search for immunostimulatory molecules and adjuvants in order to enhance or to direct an appropriate immune response against target immunogens has been a major and recurrent issue for vaccine development. In leishmaniasis, protection requires proper cellular immune response with the presence of specific CD4+ T cells and IFN-γ production and initial IL-12 production are elements required for protection. In fact, IL-12 used as an adjuvant to SLA conferred protection to mice against L. major

Acknowledgements

Teixeira CR, Cavassani KA, Teixeira MJ and Gomes RBB are recipients of CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) or CNPq (Brazilian National Research Council) scholarships. Roque-Barreira MC, Cavada BS, Silva JS, Barral A and Barral-Netto M are senior investigators of CNPq.

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