Journal Article

Roles of galectins in infection

Vasta, Gerardo R.

2009

Overview

Key Points Virtually all bacterial and eukaryotic cells, as well as many viruses, display surface carbohydrates, which have a crucial role in the establishment of host–microorganism complex interactions through their recognition by protein receptors, mainly known as lectins. Lectin–glycan interactions are ubiquitous and essential to biological systems, not simply as the 'glue' between cells, but as the initiators of a functional crosstalk that modulates their physiology and homeostatic balance. Microbial lectins, including viral haemagglutinins, bacterial adhesins and parasite lectins, are involved in host colonization, whereas some animal lectins can function as pattern recognition receptors in immune responses against microbial pathogens and parasites. Among the various lectin families, the galectins are proteins that are characterized by a unique binding-site sequence motif, affinity for β-galactosides and wide taxonomic distribution. Most metazoans are endowed with a complex galectin repertoire, with members exhibiting multiple isoforms and subtle variations in carbohydrate specificity, which together with a certain level of plasticity in sugar binding suggests they have substantial diversity in recognition properties. Galectins were initially thought to only bind endogenous 'self' glycans and mediate developmental processes, including cell differentiation and tissue organization, and more recently, regulation of immune homeostasis. In the past few years, however, it has become clear that galectins also bind non-self glycans on the surface of potentially pathogenic microorganisms (viruses, bacteria, protista and fungi) and parasitic worms, and mediate recognition and effector functions in innate immunity. Some pathogens and parasites subvert the roles of galectins as PRRs to either attach to suitable epithelia in their insect vector or final host, or to enter the host cells to proliferate and disseminate systemically. Furthermore, galectins from parasites might contribute directly or indirectly to host invasion, or downregulation of the host immune response. In summary, the recent evidence discussed in this Review indicates that host galectins can function as recognition receptors that target non-self glycans on the surfaces of viruses, bacteria, protista and helminth pathogens and parasites, and either prevent or facilitate infection. Because galectins also bind self glycans on the host cell surface as the first step in immunoregulation and developmental processes, galectins do not fit current models of innate immune self or non-self recognition or defence. Gaps in our knowledge about the diversity of the host galectins, their subcellular compartmentalization and secretion, and structural and biophysical aspects of their interactions with the microbial carbohydrate moieties warrant further investigation. The novel insights provided by the realization that galectins are directly involved in pathogen recognition has opened new avenues of research aimed at disrupting their roles in parasite–vector interactions or host invasion. Galectins are important for recognition of carbohydrate ligands during embryogenesis, development and immune regulation. In addition, recent work has shown that galectins also function as receptors for glycans expressed on the surface of potentially pathogenic microorganisms. In this Review, Gerardo Vasta discusses the roles of galectins in host immunity and how pathogens have evolved to evade or subvert galectin-mediated immune responses. Galectins, which were first characterized in the mid-1970s, were assigned a role in the recognition of endogenous ('self') carbohydrate ligands in embryogenesis, development and immune regulation. Recently, however, galectins have been shown to bind glycans on the surface of potentially pathogenic microorganisms, and function as recognition and effector factors in innate immunity. Some parasites subvert the recognition roles of the vector or host galectins to ensure successful attachment or invasion. This Review discusses the role of galectins in microbial infection, with particular emphasis on adaptations of pathogens to evasion or subversion of host galectin-mediated immune responses.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Bacterial Infections - immunology / Binding proteins / Biomedical and Life Sciences / Carbohydrates / Communicable diseases / Control / Embryonic growth stage / Galectins - chemistry / Galectins - immunology / Galectins - metabolism / Genetic aspects / Glycoproteins / Host-Pathogen Interactions - immunology / Host-Pathogen Interactions - physiology / Humans / Infections / Infectious Diseases / Lectins / Life Sciences / Medical Microbiology / Microbiology / Microorganisms / Models, Biological / Natural immunity / Oligosaccharides - chemistry / Oligosaccharides - metabolism / Parasites / Parasitology / Pathogens / Physiological aspects / Protein Binding / Proteins / review-article / Roles / Symbiosis / Virology