A Role for Insect Galectins in Parasite Survival

Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Cell (Impact Factor: 32.24). 11/2004; 119(3):329-41. DOI: 10.1016/j.cell.2004.10.009
Source: PubMed


Insect galectins are associated with embryonic development or immunity against pathogens. Here, we show that they can be exploited by parasites for survival in their insect hosts. PpGalec, a tandem repeat galectin expressed in the midgut of the sandfly Phlebotomus papatasi, is used by Leishmania major as a receptor for mediating specific binding to the insect midgut, an event crucial for parasite survival, and accounts for species-specific vector competence for the most widely distributed form of cutaneous leishmaniasis in the Old World. In addition, these studies demonstrate the feasibility of using midgut receptors for parasite ligands as target antigens for transmission-blocking vaccines.

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Available from: Carolina Barillas-Mury, Oct 02, 2015
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    • "Drosophila and sand fly galectins regulate development and de - fense against bacterial and parasitic pathogens ( Pace and Baum , 2004 ; Kamhawi et al. , 2004 "
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    ABSTRACT: Pattern recognition receptors (PRRs) detect microbial pathogens and trigger innate immune responses. Previous biochemical studies have elucidated the physiological functions of eleven PRRs in Manduca sexta but our understanding of the recognition process is still limited, lacking genomic perspectives. While 34 C-type lectin-domain proteins and 16 Toll-like receptors are reported in the companion papers, we present here 120 other putative PRRs identified through the genome annotation. These include 76 leucine-rich repeat (LRR) proteins, 14 peptidoglycan recognition proteins, 6 EGF/Nim-domain proteins, 5 β-1,3-glucanase-related proteins, 4 galectins, 4 fibrinogen-related proteins, 3 thioester proteins, 5 immunoglobulin-domain proteins, 2 hemocytins, and 1 Reeler. Sequence alignment and phylogenetic analysis reveal the evolution history of a diverse repertoire of proteins for pathogen recognition. While functions of insect LRR proteins are mostly unknown, their structure diversification is phenomenal: In addition to the Toll homologs, 22 LRR proteins with a signal peptide are expected to be secreted; 18 LRR proteins lacking signal peptides may be cytoplasmic; 36 LRRs with a signal peptide and a transmembrane segment may be non-Toll receptors on the surface of cells. Expression profiles of the 120 genes in 52 tissue samples reflect complex regulation in various developmental stages and physiological states, including some likely by Rel family transcription factors via κB motifs in the promoter regions. This collection of information is expected to facilitate future biochemical studies detailing their respective roles in this model insect. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Insect Biochemistry and Molecular Biology 02/2015; 62. DOI:10.1016/j.ibmb.2015.02.001 · 3.45 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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    • "Intriguingly, galectin-mediated bridging of L. major to host cells is also important at another point in the parasite life cycle. Valenzuela and co-workers found that a galectin homolog in the midgut of the sand fly Phlebotomus papatasi participates in binding of L. major at the procyclic phase to gut epithelial cells during infection of this obligate insect host (35). The L. major parasite replicates in the sandfly midgut and differentiates into the metacyclic phase that is highly infectious to mammalian hosts and is transmitted during insect bites. "
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    ABSTRACT: Microbe-host interactions are complex processes that are directly and indirectly regulated by a variety of factors, including microbe presentation of specific molecular signatures on the microbial surface, as well as host cell presentation of receptors that recognize these pathogen signatures. Cell surface glycans are one important class of microbial signatures that are recognized by a variety of host cell lectins. Host cell lectins that recognize microbial glycans include members of the galectin family of lectins that recognize specific glycan ligands on viruses, bacteria, fungi, and parasites. In this review, we will discuss the ways that the interactions of microbial glycans with host cell galectins positively and negatively regulate pathogen attachment, invasion, and survival, as well as regulate host responses that mitigate microbial pathogenesis.
    Frontiers in Immunology 06/2014; 5:284. DOI:10.3389/fimmu.2014.00284
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