Effective host-directed therapy for tuberculosis by targeted depletion of myeloid-derived suppressor 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 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.