['Myeloid cells encompass distinct populations with unique functions during homeostasis and disease. Recently, a novel subset of innate cells, myeloid-derived suppressor cells (MDSCs), has been described in cancer, which suppresses T-cell responses and fosters disease progression. The role of MDSCs in infection is insufficiently addressed.', 'To examine the presence and function of MDSCs during experimental pulmonary tuberculosis (TB) and further understand the immunologic consequences of direct interactions between MDSCs and lung bacterial pathogens.', 'Using cell-based approaches and experimental mouse models for pulmonary TB we characterized MDSCs as novel myeloid populations directly interacting with Mycobacterium tuberculosis (Mtb).', 'MDSCs readily phagocytosed Mtb, and released proinflammatory (IL-6, IL-1α) and immunomodulatory (IL-10) cytokines while retaining their suppressive capacity. MDSCs were identified at the site of infection in the lung in disease-resistant and -susceptible mice during pulmonary TB. Excessive MDSC accumulation in lungs correlated with elevated surface expression of IL-4Rα and heightened TB lethality, whereas targeted depletion of MDSCs ameliorated disease.'] Do lung-residing myeloid-derived suppressors display dual functionality in murine pulmonary tuberculosis?