Suppressor Cell-Depleting Immunotherapy With Denileukin Diftitox is an Effective Host-Directed Therapy for Tuberculosis

J Infect Dis. 2017 Jun 15;215(12):1883-1887. doi: 10.1093/infdis/jix208.

Abstract

Host-directed therapies that augment host immune effector mechanisms may serve as important adjunctive therapies for tuberculosis treatment. We evaluated the activity of denileukin diftitox in an acute mouse model of tuberculosis (TB) infection and analyzed the cellular composition and bacterial burden in lungs and spleens. These in vivo studies show that denileukin diftitox potentiates standard TB treatment in the mouse model, an effect which may be due to depletion of T-regulatory and myeloid-derived suppressor cells during TB infection. Our results indicate that denileukin diftitox and other suppressor cell-depleting therapies may be useful adjunctive, host-directed therapies for TB.

Keywords: Denileukin diftitox recombinant fusion protein toxin; Host-directed therapy; Immunotherapy; Tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diphtheria Toxin / therapeutic use*
  • Disease Models, Animal
  • Humans
  • Immunotherapy / methods*
  • Interleukin-2 / therapeutic use*
  • Lung / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • Myeloid-Derived Suppressor Cells / immunology*
  • Recombinant Fusion Proteins / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Tuberculosis / therapy*

Substances

  • Diphtheria Toxin
  • Interleukin-2
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • denileukin diftitox