Adjunctive Zoledronate + IL-2 administrations enhance anti-tuberculosis Vγ2Vδ2 T-effector populations, and improve treatment outcome of multidrug-resistant tuberculosis1.

Abstract

Multidrug-resistant tuberculosis (MDR-TB) is a refractory disease with high mortality rate due to no or few choices of antibiotics. Adjunctive immunotherapy may help improve treatment outcome of MDR-TB. Our decade-long studies demonstrated that phosphoantigen-specific Vγ2Vδ2 T cells play protective roles in immunity against TB. Here, we hypothesized that enhancing protective Vγ2Vδ2 T-effector cells could improve treatment outcome of MDR-TB. To address this, we employed clinically approved drugs Zoledronate (ZOL) and IL-2 to induce anti-TB Vγ2Vδ2 T-effector cells as adjunctive immunotherapy against MDR-TB infection of macaques. We found that adjunctive ZOL/IL-2 administrations during TB drugs treatment of MDR-TB-infected macaques significantly expanded Vγ2Vδ2 T cells and enhanced/sustained Vγ2Vδ2 T-effector subpopulation producing anti-TB cytokines until week 21. ZOL/IL-2 administrations, while expanding Vγ2Vδ2 T cells, significantly increased/sustained numbers of circulating CD4+ Th1 and CD8+ Th1-like effector populations, with some γδ T- or αβ T-effector populations trafficking to airway at week 3 until week 19 or 21 after MDR-TB infection. Adjunctive ZOL/IL-2 administrations after MDR-TB infection led to lower bacterial burdens in lungs than TB drugs alone, IL-2 alone or saline controls, and resulted in milder MDR-TB pathology/lesions. Thus, adjunctive Zoledronate + IL-2 administrations can enhance anti-TB Vγ2Vδ2 T- and αβ T-effector populations, and improve treatment outcome of MDR-TB.

• Authors: Hongbo Shen, Enzhuo Yang, Ming Guo, Rui Yang, Guixian Huang, Ying Peng, Wei Sha, Feifei Wang, Ling Shen
• Journal: Emerging microbes & infections (Emerg Microbes Infect) Vol. 11 Issue 1 Pg. 1790-1805 (Dec 2022) ISSN: 2222-1751 [Electronic] United States
• PMID: 35765887 (Publication Type: Journal Article)

Chemical References

• Interleukin-2
• Zoledronic Acid

Topics

• Animals
• Interleukin-2
• Macaca
• Mycobacterium tuberculosis
• Treatment Outcome
• Tuberculosis (microbiology)
• Tuberculosis, Multidrug-Resistant (drug therapy)
• Zoledronic Acid