Okumura, C. Y., Baum, L. G. & Johnson, P. J. Galectin-1 on cervical epithelial cells is a receptor for the sexually transmitted human parasite Trichomonas vaginalis. Cell. Microbiol. 1, 2078-2090

Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Cellular Microbiology (Impact Factor: 4.92). 10/2008; 10(10):2078-90. DOI: 10.1111/j.1462-5822.2008.01190.x
Source: PubMed


The extracellular protozoan parasite Trichomonas vaginalis causes the most prevalent non-viral sexually transmitted human infection, yet the pathogenesis of infection is poorly understood, and host cell receptors have not been described. The surface of T. vaginalis is covered with a glycoconjugate called lipophosphoglycan (LPG), which plays a role in the adherence and cytotoxicity of parasites to human cells. T. vaginalis LPG contains high amounts of galactose, making this polysaccharide a candidate for recognition by the galactose-binding galectin family of lectins. Here we show that galectin-1 (gal-1) is expressed by human cervical epithelial cells and binds T. vaginalis LPG. Gal-1 binds to parasites in a carbohydrate-dependent manner that is inhibited in the presence of T. vaginalis LPG. Addition of purified gal-1 to cervical epithelial cells also enhances parasite binding, while a decrease in gal-1 expression by small interfering RNA (siRNA) transfection decreases parasite binding. In contrast, the related galectin-7 (gal-7) does not bind T. vaginalis in a carbohydrate-dependent manner, and is unable to mediate attachment of parasites to host cells. Our data are consistent with the presence of multiple host cell receptors for T. vaginalis of which gal-1 is the first to be identified and highlight the importance of glycoconjugates in host-pathogen interactions.

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    • "Interestingly, we found that most of the TvTSPs analysed were up-regulated upon contact with VECs, suggesting a role for these proteins in host : parasite interaction. Since in vitro attachment of the parasites is mostly completed within ∼ 20 min of exposure to the VECs (Okumura et al., 2008), the pattern of up-regulation suggests TvTSPs plays a role in events occurring downstream of adherence. It is important to note that while most of the TvTSP genes we found were up regulated upon exposure of B7RC2 strain to host cells, these genes were not reported in the up regulated group in the Gould et al. analysis (Gould et al., 2013). "
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    ABSTRACT: The parasite Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection. Here, we report the cellular analysis of T. vaginalis tetraspanin family (TvTSPs). This family of membrane proteins has been implicated in cell adhesion, migration and proliferation in vertebrates. We found that the expression of several members of the family is up-regulated upon contact with vaginal ectocervical cells (VECs). We demonstrate that most TvTSPs are localized on the surface and intracellular vesicles and that the C-terminal intracellular tails of surface TvTSPs are necessary for proper localization. Analyses of full length TvTSP8 and a mutant that lacks the C-terminal tail indicates that surface localized TvTSP8 is involved in parasite aggregation, suggesting a role for this protein in parasite: parasite interaction. This article is protected by copyright. All rights reserved.
    Cellular Microbiology 02/2015; 17(8). DOI:10.1111/cmi.12431 · 4.92 Impact Factor
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    • "The multivalency of galectins resulting from their oligomerization is not only key to their cooperative binding to complex carbohydrate ligands and their ability to crosslink surface glycans and form lattices (Vasta et al., 2004; Rabinovich et al., 2007), but would also enable galectins to facilitate the attachment of pathogens to the cell surface (Ahmad et al., 2004; Nieminen et al., 2007; Vasta, 2009). This subversion of galectins functions as PRRs has already been reported for the galectin-mediated attachment of viruses (Ouellet et al., 2005; Garner et al., 2010; St-Pierre et al., 2011; Yang et al., 2011), bacteria (Okumura et al., 2008), and eukaryotic parasites (Kamhawi et al., 2004). Prior studies have provided evidence that the release of sialic acid by the activity of the IAV neuraminidase promotes the adhesion of S. pneumoniae to airway epithelial cells in the form of a biofilm, that makes the pathogen less accessible to host factors and antibiotics and facilitates host invasion (Trappetti et al., 2009). "
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    ABSTRACT: The continued threat of worldwide influenza pandemics, together with the yearly emergence of antigenically drifted influenza A virus (IAV) strains, underscore the urgent need to elucidate not only the mechanisms of influenza virulence, but also those mechanisms that predispose influenza patients to increased susceptibility to subsequent infection with Streptococcus pneumoniae. Glycans displayed on the surface of epithelia that are exposed to the external environment play important roles in microbial recognition, adhesion, and invasion. It is well established that the IAV hemagglutinin and pneumococcal adhesins enable their attachment to the host epithelia. Reciprocally, the recognition of microbial glycans by host carbohydrate-binding proteins (lectins) can initiate innate immune responses, but their relevance in influenza or pneumococcal infections is poorly understood. Galectins are evolutionarily conserved lectins characterized by affinity for β-galactosides and a unique sequence motif, with critical regulatory roles in development and immune homeostasis. In this study, we examined the possibility that galectins expressed in the airway epithelial cells might play a significant role in viral or pneumococcal adhesion to airway epithelial cells. Our results in a mouse model for influenza and pneumococcal infection revealed that the murine lung expresses a diverse galectin repertoire, from which selected galectins, including galectin 1 (Gal1) and galectin 3 (Gal3), are released to the bronchoalveolar space. Further, the results showed that influenza and subsequent S. pneumoniae infections significantly alter the glycosylation patterns of the airway epithelial surface and modulate galectin expression. In vitro studies on the human airway epithelial cell line A549 were consistent with the observations made in the mouse model, and further revealed that both Gal1 and Gal3 bind strongly to IAV and S. pneumoniae, and that exposure of the cells to viral neuraminidase or influenza infection increased galectin-mediated S. pneumoniae adhesion to the cell surface. Our results suggest that upon influenza infection, pneumococcal adhesion to the airway epithelial surface is enhanced by an interplay among the host galectins and viral and pneumococcal neuraminidases. The observed enhancement of pneumococcal adhesion may be a contributing factor to the observed hypersusceptibility to pneumonia of influenza patients.
    Molecular Immunology 01/2015; 65(1):1-16. DOI:10.1016/j.molimm.2014.12.010 · 2.97 Impact Factor
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    • "Regarding Gal-1, although this lectin is a cervical epithelial cell receptor for the sexually transmitted parasite Trichomonas vaginalis and can promote HIV-1 absorption to CD4+ T cells and macrophages facilitating the infection [36], [37], in this work we observed no effect on C. rodentium colonisation of the mucosal epithelium. "
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    ABSTRACT: Despite their abundance at gastrointestinal sites, little is known about the role of galectins in gut immune responses. We have therefore investigated the Citrobacter rodentium model of colonic infection and inflammation in Galectin-1 or Galectin-3 null mice. Gal-3 null mice showed a slight delay in colonisation after inoculation with C. rodentium and a slight delay in resolution of infection, associated with delayed T cell, macrophage and dendritic cell infiltration into the gut mucosa. However, Gal-1 null mice also demonstrated reduced T cell and macrophage responses to infection. Despite the reduced T cell and macrophage response in Gal-1 null mice, there was no effect on C. rodentium infection kinetics and pathology. Overall, Gal-1 and Gal-3 play only a minor role in immunity to a gut bacterial pathogen.
    PLoS ONE 09/2014; 9(9):e107933. DOI:10.1371/journal.pone.0107933 · 3.23 Impact Factor
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