Role of galectin-3 in the Cryptococcus neoformans infection

Abstract

Cryptococcus neoformans is the causative agent of cryptococcosis and a major pathogen for immunosuppressed individuals. C. neoformans represents a unique model in cell biology studies since it is the only eukaryotic pathogen with a polysaccharide capsule, furthermore produces vesicles containing its major virulence factor. These vesicles cross the cell wall to reach the extracellular space, where the polysaccharide is supposedly used for capsule growth or delivered into host tissues. Galectin-3, a glycan-binding protein, controls a broad spectrum of immunological functions, including cell adhesion, migration, activation, apoptosis and cytokine secretion within innate and adaptive immune compartments. During postdoctoral stage in the Albert Einstein College of Medicine of New York, we have verified that galectin-3 has lytic effect on extracellular vesicles of C. neoformans and we also have detected elevated levels of galectin-3 in the course of cryptococcosis murine experimental. These observations motivate the proposal to study the galectin-3 interference in the course of infection by C. neoformans, furthermore to better understand the effect of galectin-3 on the extracellular vesicles produced by C. neoformans. More specifically, we propose to do the following aims: (1) to dissect the responsible interactions by lytic effect of galectin-3 on the extracelular vesicles from C. neoformans, (2) to investigate the regulated expression and distribution of galectin-3 in murine tissues infected by C. neoformans, (3) to compare the survival of C. neoformans infection between wild and knockout (galectin-3 KO) mice, (4) to investigate the role of galectin-3 in the course of C. neoformans infection in mice through histopathological and immunological parameters, (5) to analyze comparatively the genic profile of the host innate immune response, during cryptococcosis by PCR Array, according to genic modulation to antifungal response, as well as in addition to compare with the genic modulation of the galectin-3 KO mice infected by C. neoformans. Our expectation is that galectin-3 may be responsible for important functions on the infection process by C. neoformans. (AU)