Galectins in Host–Pathogen Interactions: Structural, Functional and Evolutionary Aspects

Abstract

Galectins are a family of ß-galactoside-binding lectins characterized by a unique sequence motif in the carbohydrate recognition domain, and evolutionary and structural conservation from fungi to invertebrates and vertebrates, including mammals. Their biological roles, initially understood as limited to recognition of endogenous (“self”) carbohydrate ligands in embryogenesis and early development, dramatically expanded in later years by the discovery of their roles in tissue repair, cancer, adipogenesis, and regulation of immune homeostasis. In recent years, however, evidence has also accumulated to support the notion that galectins can bind (“non-self”) glycans on the surface of potentially pathogenic microbes, and function as recognition and effector factors in innate immunity. Thus, this evidence has established a new paradigm by which galectins can function not only as pattern recognition receptors but also as effector factors, by binding to the microbial surface and inhibiting adhesion and/or entry into the host cell, directly killing the potential pathogen by disrupting its surface structures, or by promoting phagocytosis, encapsulation, autophagy, and pathogen clearance from circulation. Strikingly, some viruses, bacteria, and protistan parasites take advantage of the aforementioned recognition roles of the vector/host galectins, for successful attachment and invasion. These recent findings suggest that galectin-mediated innate immune recognition and effector mechanisms, which throughout evolution have remained effective for preventing or fighting viral, bacterial, and parasitic infection, have been “subverted” by certain pathogens by unique evolutionary adaptations of their surface glycome to gain host entry, and the acquisition of effective mechanisms to evade the host’s immune responses.