SEEING STRANGERS OR ANNOUNCING DANGER: GALECTINS AS A NOVEL TYPE OF IMMUNOMODULATORS

S. SATO; G. RABINOVICH

BOSTON, MA

Simposio; 1ST INTERNATIONAL SYMPOSIUM ON GALECTINS; 2007

AMERICAN CHEMICAL ASSOCIATION

Seeing strangers or announcing ‘’Danger’’: Galectins as a novel type of immunomodulator Gabriel Rabinovich* and Sachiko Sato† *Institute of Biology and Experimental Medicine, IBYME/ CONICET and University of Buenos Aires. Buenos Aires, Argentina † From Glycobiology Laboratory, Research Center for Infectious Diseases, Faculty of Medicine, Laval University, Québec, Canada When microorganisms invade or aberrant cells emerge, immunity recognizes these events and tries to respond to maintain host integrity.  Innate immunity needs to measure not only “non-selfness” of those entities, but also estimate the level of “danger” they represent for the host, using a machinery that can detect a unique set of endogenous cytosolic molecules. Recent works suggest that galectins could be a part of this machinery. Investigation on galectins revealed that in the context of pneumonia, galectin-3 acts as a unique adhesion molecule for neutrophil recruitment during pathogenic Streptococcal pneumoniae, but not for non-pathogenic E. coli. Pathogens and cancer cells can also exploit this machinery. Indeed, HIV-1 uses galectin-1 to facilitate its infections of susceptible cell through the stabilization of the HIV adsorption step. In addition, cancer cells also utilize galectin-1 to establish a novel immune escape strategy through the induction of immunosuppression. Investigations have revealed that T helper (TH)1- and TH2-promoting stimuli can differentially regulate the glycosylation pattern of T-helper cells and modulate their susceptibility to galectin-1. While TH1-differentiated cells express the repertoire of cell surface glycans that are critical for galectin-1 binding and cell death, TH2 cells are protected from galectin-1 through differential sialylation of cell surface glycoproteins. Understanding the paradigms by which protein-sugar interactions regulate tumor-immune escape and immune response to pathogenic infection might contribute to the design of rational anti-tumor and anti-infection strategies.