Abstract
Mycobacteria have a cell envelope that can act as a shield against host defense. This study shows that mycobacteria survive in host macrophages by targeting the innate host receptor dectin-1 through a noncanonical ligand. Compared with wild-type (WT) mice, dectin-1-deficient mice were more resistant to infection to mycobacteria. Dectin-1-deficient mice presented with substantially reduced bacterial burdens, inflammatory cytokines, and infiltrating myeloid cells, such as neutrophils and macrophages. Intracellular survival of these bacteria was reduced in macrophages derived from dectin-1-deficient mice compared with those from WT mice. Cellular characterization of mycobacteria-infected macrophages indicated that the presence of dectin-1 altered phagosomal maturation and association with markers of autophagy. Activity-based purification and nuclear magnetic resonance spectrometry identified branched α-glucan as the dectin-1 mycobacterial ligand. This branched glucan was essential for activating dectin-1. These results show that mycobacterial α-glucan targets dectin-1 to facilitate intracellular bacterial survival.