UC Berkeley

Macrophages employ an array of receptors to detect and eliminate intracellular pathogens that access the cytosol. Galectins represent one such class of receptors, and activate membrane repair or autophagy-mediated degradation of ruptured organelles. In macrophages, Gal-3, -8, and -9 promote innate immune signaling following recognition of luminal host glycoproteins in damaged pathogen-containing phagosomes, but their contributions to immunity during infection in vivo remain unclear. We found that Gal-9 interacts directly with the intracellular pathogens, Mycobacterium tuberculosis (Mtb) and Salmonella typhimurium. This interaction was dependent upon Gal-9 carbohydrate-binding and occurred both in vitro and in vivo. To determine the contribution of the galectin system to host resistance in vivo, we generated Gal-3, -8, -9 triple knockout mice (TKO) and challenged these mice with a panel of intracellular bacteria. We found that galectin deficiency leads to impairments in bacterial growth restriction and CD4 T cell activation during chronic Mtb infection. However, during acute infection with Mtb, S. typhimurium, or L. monocytogenes, TKO mice exhibited normal resistance. In addition, we found that galectin deficiency in macrophages leads to inefficient clearance of Mtb from the cytosol, despite TKO macrophages exhibiting normal bacterial growth restriction. Collectively, our findings indicate that the galectin system is dispensable for protection against acute bacterial infection but necessary for full resistance to chronic tuberculosis infection.