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: 33.12). 11/2004; 119(3):329-41. DOI: 10.1016/j.cell.2004.10.009
Source: PubMed

ABSTRACT 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, Jul 08, 2015
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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 · 3.00 Impact Factor
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    • "Previous molecular studies contributed to understanding the events that occur during the establishment of Leishmania infection in sandflies (Ramalho-Ortigao et al. 2010). Leishmania molecules such as LPG (Svarovska et al. 2010), which binds to the sandfly midgut galectin receptor PpGalec (Kamhawi et al. 2004), sandfly digestive enzymes (Sant'Anna et al. 2009, Telleria et al. 2010) and the peritrophic matrix (PM) (Pimenta et al. 1997) contribute to the success of the infection. "
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    ABSTRACT: Lutzomyia longipalpis is the most important vector of visceral leishmaniasis in Brazil. When female sandflies feed on blood, a peritrophic matrix (PM) is formed around the blood bolus. The PM is secreted by midgut cells and composed of proteins, glycoproteins and chitin microfibrils. The PM functions as both a physical barrier against pathogens present in the food bolus and blood meal digestion regulator. Previous studies of mosquitoes and sandflies have shown that the absence of a PM, resulting from adding an exogenous chitinase to the blood meal, accelerates digestion. In the present study, we analysed biological factors associated with the presence of a PM in L. longipalpis females. Insects fed blood containing chitinase (BCC) accelerated egg-laying relative to a control group fed blood without chitinase. However, in the BCC-fed insects, the number of females that died without laying eggs was higher and the number of eggs laid per female was lower. The eggs in both groups were viable and generated adults. Based on these data, we suggest that the absence of a PM accelerates nutrient acquisition, which results in premature egg production and oviposition; however, the absence of a PM reduces the total number of eggs laid per female. Reduced fecundity in the absence of a PM may be due to inefficient nutrient conversion or the loss of the protective role of the PM.
    Memórias do Instituto Oswaldo Cruz 06/2012; 107(4):543-5. DOI:10.1590/S0074-02762012000400016 · 1.57 Impact Factor
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    • "Moreover, no infectious metacyclic forms were detected from the flies fed on anti-PpGalec sera (Kamhawi et al. 2004). "
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