Research review paperProtozoa lectins and their role in host–pathogen interactions
Introduction
Lectins are proteins/glycoproteins of non-immune origin which agglutinate cells including erythrocytes, lymphocytes and microbial cells, or precipitate glycoconjugates through sugar specific binding sites (Goldstein and Poretz, 1986, Sharon and Lis, 2003). They bind non-covalently to specific sugars on apposing cells and mediate cell–cell interactions. Exceptionally, some lectins bind to cell surfaces but do not result in agglutination (non-agglutinating lectins), as affinity of lectin molecule to its receptor varies according to the variations in their carbohydrate receptor (Northrop and Connor, 2008). Toxic non-agglutinating lectins and non-toxic agglutinating lectins have been reported from seed extracts of Ricinus communis (Olsnes and Pihl, 1973). Due to specific binding of both these proteins to animal cell surfaces via specific sugar residues, these have been properly termed as lectins (Callow, 1976). Haemagglutination is a major attribute of lectin activity and has been classically and routinely used for detection and characterization of lectins (Ambrosi et al., 2005). However, cell agglutination is not a defining feature of lectins and a broader definition includes carbohydrate binding proteins other than enzyme or antibody (Barondes, 1988). Peumans and Van Damme (1995) concluded that the prerequisite for a protein to be termed as lectin is presence of atleast one non-catalytic domain that binds to a carbohydrate, specifically and reversibly. Certain carbohydrate binding proteins do not precipitate glycoconjugates or agglutinate cells due to presence of single carbohydrate binding site. Thus various proteins behaving differently in terms of their agglutination and/or glycoconjugate precipitation are included under the term “lectins” (Peumans and Van Damme, 1995).
Owing to their ability to identify subtle variations in carbohydrate structures, lectins have been the subject of intense research. Lectins are excellent candidates to mediate parasite interactions with complementary ligands on host cells and thus play a significant role in cell–cell interactions (Singh et al., 2011a, Singh and Walia, 2014a). Lectins from microbes have been attributed with varied biomedical applications (Singh and Bhari, 2013, Singh et al., 2010, Singh et al., 2015a, Singh et al., 2016a, Tiwary and Singh, 1998, Tiwary and Singh, 1999). A panorma of microfungal lectins possess antimicrobial (Singh et al., 2013b, Singh and Thakur, 2014), mitogenic (Singh and Walia, 2014b, Singh et al., 2014, Singh et al., 2015b, Singh et al., 2015c) and immunomodulatory (Singh et al., 2011b) activities, and also have potential roles in mycoparasitism and host–parasite interactions (Singh et al., 2011c). Based on their unique carbohydrate binding specificities, a number of lectins have been reported from plants, animals, fungi, bacteria, protozoa and viruses etc. (Singh et al., 1999). Data survey from various internet sources reveals that protozoal lectins constitute only 2.2% of total microbial lectins (Fig. 1). A number of protozoa such as Entamoeba (Petri et al., 1987), Giardia (Ward et al., 1990), Cryptosporidium (Joe et al., 1994), Trichomonas, (Roussel et al., 1991) and Plasmodium (Jungery, 1985) etc. possess lectin-like proteins. In protozoans, lectins mediate parasite adherence to host cells, thus play a significant role in various cell-to-cell interactions (Thea et al., 1992), in binding to red blood cells (Schoppert et al., 1996), and in cytopathogenicity (Petri et al., 2002, Roussel et al., 1991). Keeping in view the pivotal role of lectins in protozoa pathogenesis, the current review focusses on haemagglutination activity, carbohydrate specificity and characteristics of various protozoa lectins and also lays emphasis on role of these lectins in disease establishment and pathogenesis.
Section snippets
Haemagglutination activity of protozoa lectins
A remarkable property of lectins is to agglutinate human blood type erythrocytes, and based on their specificity to agglutinate, they are classified as specific/non-specific. Erythrocyte susceptibility to certain lectins occurs upon its mild enzymatic treatment due to exposure of masked sites on/within erythrocyte membrane. Haemagglutination activity of various protozoan lectins is enlisted in Table 1. Surface membrane-associated lectin from Giardia lamblia trophozoites avidly agglutinates
Carbohydrate specificity of the protozoa lectins
Various glycoproteins, glycolipids and proteoglycans envelope the host gastrointestinal tract cell surface which act as a major site for microbial infection. Zoonostic pathogens such as E. histolytica, Giardia, Cryptosporidium, Toxoplasma gondii etc. invade and colonize alimentary tract target tissue in host cells. Lectins bind reversibly to carbohydrates with high specificity (Sharon and Lis, 2003). Carbohydrate specificity of various protozoa lectins is tabulated in Table 2. Based on their
Characteristics of protozoa lectins
A panorama of lectins has been reported from various protozoan species which have been purified and characterized to reveal its potential role in disease pathogenesis (Table 3).
Role of lectins from pathogenic protozoa in pathogenesis
In a number of parasitic protozoa, lectins or carbohydrate-binding proteins have been identified which are involved in mediating protozoa attachment to host cells (Table 4). In protozoan parasites such as P. falciparum, T. cruzi, E. histolytica and G. lamblia, lectins mediate cell–cell interactions (Chang, 1981, Crane and Dvorak, 1982, Lev et al., 1986, Ravdin et al., 1989). Owing to their role in host–parasite interactions, lectins act as valuable tools to study pathogenesis of infection. To
Conclusions
This review vividly illustrates the key features relating to the characterization and carbohydrate specificity of the protozoa lectins currently known, which are crucial in disease establishment. Protozoan parasites possess cell surface associated lectins which mediate parasite attachment to host cells. Various protozoan lectins exhibit specificity among wide range of simple and substituted sugars as well as complex glycoproteins. Lectin–carbohydrate interaction involvement in sporozoite
Declaration of interest
Authors have no conflict of interest.
Acknowledgement
A.K. Walia is thankful to University Grant Commission, New Delhi, Government of India for providing financial assistance in form of Maulana Azad National Fellowship.
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