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

Autor:	Murphy, Sadiya Parveen, William R. Bishai, Cardin M, Michael E. Urbanowski, Shichun Lun
Rok vydání:	2020
Předmět:	Diphtheria toxin Tuberculosis biology business.industry biology.organism_classification medicine.disease Fusion protein law.invention Mycobacterium tuberculosis law Cancer research Myeloid-derived Suppressor Cell medicine Suppressor Receptor business Interleukin 4
DOI:	10.1101/2020.12.10.420224
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::3ed95d8e271e91f7e1304b9cf2d45f7d https://doi.org/10.1101/2020.12.10.420224 Zobrazit plný text záznamu