Effective host-directed therapy for tuberculosis by targeted depletion of myeloid-derived suppressor cells and related cells using a diphtheria toxin-based fusion protein.

Myeloid-derived suppressor cells (MDSCs) are present in elevated numbers in TB patients and have been found to be permissive for Mycobacterium tuberculosis (Mtb) proliferation. To determine whether depletion of MDSCs may improve host control of TB, we used a novel diphtheria toxin-based fusion protein known as DABIL-4 that targets and depletes IL-4-receptor positive cells. We show that DABIL-4 depletes both PMN-MDSCs and M-MDSC, increases IFNγ + T-cells, and reduces the lung bacillary burden in the mouse TB model. These results indicate that MDSC-depleting therapies targeting the IL-4 receptor are beneficial in TB and offer an avenue towards host-directed TB therapy.