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

ABSTRACT 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 in the mouse TB model, and that it reduces the lung bacillary burden of Mtb . These results indicate that MDSC-depleting therapies targeting the IL4 receptor are beneficial in TB and offer an avenue towards host-directed TB therapy.