Galectins as self/non-self recognition receptors in innate and adaptive immunity: An unresolved paradox

Gerardo R. Vasta, Hafiz Ahmed, Mihai Nita-Lazar, Aditi Banerjee, Marta Pasek, Surekha Shridhar, Prasun Guha, José A. Fernández-Robledo

Research output: Contribution to journalReview article

Abstract

Galectins are characterized by their binding affinity for β-galactosides, a unique binding site sequence motif, and wide taxonomic distribution and structural conservation in vertebrates, invertebrates, protista, and fungi. Since their initial description, galectins were considered to bind endogenous ("self") glycans and mediate developmental processes and cancer. In the past few years, however, numerous studies have described the diverse effects of galectins on cells involved in both innate and adaptive immune responses, andthe mechanistic aspects of their regulatory roles in immune homeostasis. More recently, however, evidence has accumulated to suggest that galectins also bind exogenous ("non-self") glycans on the surface of potentially pathogenic microbes, parasites, and fungi, suggesting that galectins can function as pattern recognition receptors (PRRs) in innate immunity. Thus, a perplexing paradox arises by the fact that galectins also recognize lactosamine- containing glycans on the host cell surface during developmental processes and regulation of immune responses. According to the currently accepted model for non-self recognition, PRRs recognize pathogens via highly conserved microbial surface molecules of wide distribution such as LPS or peptidoglycan (pathogen-associated molecular patterns; PAMPs), which are absent in the host. Hence, this would not apply to galectins, which apparently bind similar self/non-self molecular patterns on host and microbial cells.This paradox underscores first, an oversimplification in the use of the PRR/PAMP terminology. Second, and most importantly, it reveals significant gaps in our knowledge about the diversity of the host galectin repertoire, and the subcellular targeting, localization, and secretion. Furthermore, our knowledge about the structural and biophysical aspects of their interactions with the host and microbial carbohydrate moieties is fragmentary, and warrants further investigation.

Original languageEnglish (US)
Article numberArticle 199
JournalFrontiers in immunology
Volume3
Issue numberJUL
DOIs
StatePublished - 2012

Keywords

  • C-type lectin
  • Galectin
  • Glycan ligands
  • Microbial recognition

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Vasta, G. R., Ahmed, H., Nita-Lazar, M., Banerjee, A., Pasek, M., Shridhar, S., Guha, P., & Fernández-Robledo, J. A. (2012). Galectins as self/non-self recognition receptors in innate and adaptive immunity: An unresolved paradox. Frontiers in immunology, 3(JUL), [Article 199]. https://doi.org/10.3389/fimmu.2012.00199