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IL-10 Modulation Increases Pyrazinamide's Antimycobacterial Efficacy against Mycobacterium tuberculosis Infection in Mice.

Varun DwivediShalini GautamGillian BeamerPaul C StrombergColwyn A HeadleyJoanne Turner
Published in: ImmunoHorizons (2023)
Mechanisms to shorten the duration of tuberculosis (TB) treatment include new drug formulations or schedules and the development of host-directed therapies (HDTs) that better enable the host immune system to eliminate Mycobacterium tuberculosis. Previous studies have shown that pyrazinamide, a first-line antibiotic, can also modulate immune function, making it an attractive target for combinatorial HDT/antibiotic therapy, with the goal to accelerate clearance of M. tuberculosis. In this study, we assessed the value of anti-IL-10R1 as an HDT along with pyrazinamide and show that short-term anti-IL-10R1 blockade during pyrazinamide treatment enhanced the antimycobacterial efficacy of pyrazinamide, resulting in faster clearance of M. tuberculosis in mice. Furthermore, 45 d of pyrazinamide treatment in a functionally IL-10-deficient environment resulted in sterilizing clearance of M. tuberculosis. Our data suggest that short-term IL-10 blockade with standard TB drugs has the potential to improve clinical outcome by reducing the treatment duration.
Keyphrases
  • mycobacterium tuberculosis
  • pulmonary tuberculosis
  • type diabetes
  • hiv aids
  • stem cells
  • risk assessment
  • adipose tissue
  • big data
  • replacement therapy
  • skeletal muscle
  • hiv infected
  • mesenchymal stem cells
  • deep learning