Targeting the Immune System with Plant Lectins to Combat Microbial Infections

Abstract

The arsenal of drugs available to treat infections caused by eukaryotic and prokaryotic microbes has been declining exponentially due to antimicrobial resistance phenomenon, leading to an urgent need to develop new therapeutic strategies. Host-directed immunotherapy has been reported as an attractive option to treat microbial infections. It consists in the improvement of host defenses by increasing the expression of inflammatory mediators and/or controlling of inflammation-induced tissue injury. Although the in vitro antimicrobial and immunomodulatory activities of lectins have been extensively demonstrated, few studies have evaluated their in vivo effects on experimental models of infections. This review aims to highlight the experimental use of immunomodulatory plant lectins to improve the host immune response against microbial infections. Lectins have been used in vivo both prophylactically and therapeutically resulting in the increased survival of mice under microbial challenge. Other studies successfully demonstrated that lectins could be used in combination with parasite antigens in order to induce a more efficient immunization. Therefore, these plant lectins represent new candidates for management of microbial infections. Furthermore, immunotherapeutic studies have improved our knowledge about the mechanisms involved in host-pathogen interactions, and may also help in the discovery of new drug targets.

Keywords: adjuvants; host–parasite interaction; immunization; immunomodulatory lectins; new treatments.

FIGURE 1

Schematic representation of studies employing plant lectins in experimental bacterial infection. (A) After inoculation, bacteria can invade cell and provoke damage by releasing different virulence factors and inducing an exacerbated immune response. The final effect is organ dysfunction and animal death. (B) Administration of a lectin (for example, ConA) after infection could improve mice response against bacterial infection and increase the animal survival. (C) Pre-treatment of animal with lectin (such as ConBr) induces an immune response able to protect against bacterial virulence resulting in the improvement of animal survival. The proteins structures were obtained from Protein Data Bank, the ID codes are 4PF5 and 4P14 for ConA and ConBr, respectively.

FIGURE 2

An overview of the effects of Cramoll alone or in combination with fluconazole in an experimental cryptococcosis model. (A) Cryptococcus gattii provokes tissue damage and organ dysfunction by releasing different virulence factors and inducing an exacerbated immune response. (B) When Cramoll was administrated alone (B) or in combination with fluconazole (C), infected mice exhibited increased ratios of survival and reduced levels of morbidity and behavior alteration. The PDB code for Cramoll structure is 1MVQ.

FIGURE 3

Application of Jacalin as adjuvant for immunization against T. cruzi. (A) Mice were immunized with T. cruzi antigens and after 1 month infected with T. cruzi. The antigens failed in inducing an efficient protective humoral response. (B) Animal subjected to immunization with jacalin (PDB ID 1JAC) plus T. cruzi antigens showed higher antibodies titers and lower parasitemia levels than mice that received only T. cruzi antigens.

FIGURE 4

Therapeutic effects of plant lectins in protozoan infections. Experimental exposure of mice to protozoan results in cell damage, tissue destruction, and consequently animal death (A). Lectins can improve protozoan-infected animal survival by increasing production of Th1 cytokines. The induction of pro-inflammatory response leads to a reduction in parasite levels and organ dysfunction (B). The structure of Artin M was obtained from PDB (ID: 1J4U).