Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenic yeast Candida albicans displays at its cell surface beta-1,2 oligomannosides (beta-1,2-Mans). In contrast to the ubiquitous alpha-Mans, beta-1,2-Mans bind to galectin-3, a major endogenous lectin expressed on epithelial cells. The specific role of beta-1,2-Mans in colonization of the gut by C. albicans was assessed in a mouse model. A selected virulent strain of C. albicans (expressing more beta-1,2-Man epitopes) induced more intense and sustained colonization than an avirulent strain (expressing less beta-1,2-Man epitopes). Synthetic (Sigma) beta-and alpha-linked tetramannosides with antigenicities that mimicked the antigenicities of C. albicans-derived oligomannosides were then constructed. Oral administration of Sigmabeta-1,2-Man (30 mg/kg of body weight) prior to inoculation with the virulent strain resulted in almost complete eradication of yeasts from stool samples, whereas administration of Sigmaalpha-Man at the same dose did not. As most cases of human systemic candidiasis are endogenous in origin, this first demonstration that a synthetic analogue of a yeast adhesin can prevent yeast colonization in the gut opens the possibility of new prophylactic strategies.
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PMID:Synthetic analogues of beta-1,2 oligomannosides prevent intestinal colonization by the pathogenic yeast Candida albicans. 1243 90

Invasive candidiasis is a leading cause of nosocomial bloodstream infection. Neutrophils are the important effector cells in host resistance to candidiasis. To investigate the modulation of neutrophil fungicidal function will advance our knowledge on the control of candidiasis. While recombinant galectin-3 enhances neutrophil phagocytosis of Candida, we found that intracellular galectin-3 downregulates neutrophil fungicidal functions. Co-immunoprecipitation and immunofluorescence staining reveal that cytosolic gal3 physically interacts with Syk in neutrophils after Candida stimulation. Gal3-/- neutrophils have higher level of Syk activation as well as greater abilities to generate reactive oxygen species (ROS) and kill Candida than gal3+/+ cells. While galectin-3 deficiency modulates neutrophil and macrophage activation and the recruitment of monocytes and dendritic cells, the deficiency does not affect the numbers of infiltrating neutrophils or macrophages. Galectin-3 deficiency ameliorates systemic candidiasis by reducing fungal burden, renal pathology, and mortality. Adoptive transfer experiments demonstrate that cell intrinsic galectin-3 negatively regulates neutrophil effector functions against candidiasis. Reducing galectin-3 expression or activity by siRNA or gal3 inhibitor TD139 enhances human neutrophil ROS production. Mice treated with TD139 have enhanced ability to clear the fungus. Our work unravels the mechanism by which galectin-3 regulates Syk-dependent neutrophil fungicidal functions and raises the possibility that blocking gal3 in neutrophils may be a promising therapeutic strategy for treating systemic candidiasis.
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PMID:Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of Candida by Modulating CR3 Downstream Syk Activation. 2821 27