Gr-1dimCD11b+ Immature Myeloid-Derived Suppressor Cells but Not Neutrophils Are Markers of Lethal Tuberculosis Infection in Mice

Tuberculosis (TB) disease may progress at different rates and have different outcomes. Neutrophils have been implicated in TB progression; however, data on their role during TB are controversial. In this study, we show that in mice, TB progression is associated with the accumulation of cells that express neutrophilic markers Gr-1 and Ly-6G but do not belong to conventional neutrophils. The cells exhibit unsegmented nuclei, have Gr-1(dim)Ly-6G(dim)CD11b(+) phenotype, and express F4/80, CD49d, Ly-6C, CD117, and CD135 markers characteristic not of neutrophils but of immature myeloid cells. The cells accumulate in the lungs, bone marrow, spleen, and blood at the advanced (prelethal) stage of Mycobacterium tuberculosis infection and represent a heterogeneous population of myeloid cells at different stages of their differentiation. The accumulation of Gr-1 dim CD11b(+) cells is accompanied by the disappearance of conventional neutrophils (Gr-1(hi) Ly-6G (hi)-expressing cells). The Gr-1(dim)CD11b(+) cells suppress T cell proliferation and IFN-gamma production in vitro via NO-dependent mechanisms, that is, they exhibit characteristics of myeloid-derived suppressor cells. These results document the generation of myeloid-derived suppressor cells during TB, suggesting their role in TB pathogenesis, and arguing that neutrophils do not contribute to TB pathology at the advanced disease stage.