Immunomodulatory nanoparticles induce autophagy in macrophages and reduce mycobacterium tuberculosis burden in the lungs of mice

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Date

2025

Journal Title

Journal ISSN

Volume Title

Publisher

American Chemical Society

Abstract

Tuberculosis (TB) is the leading cause of death frominfectious disease. Macrophages are the primary immune respondersand become the primary host cells for the causative agentMycobacterium tuberculosis. Following the uptake of M. tuberculosis,the inherent antimicrobial action of macrophages is dampened,enabling the bacterium to reside within these cells and multiply.Rising resistance of M. tuberculosis to antibiotics has led to theinvestigation of novel approaches for the treatment of TB. Here, wereport a host-directed approach, employing biomimetic Curdlanpoly(lactic-co-glycolic acid) (C-PLGA) nanoparticles (NPs), andexamine autophagy induction in infected macrophages, eradication ofM. tuberculosis and immune modulation in a mouse model. Wedemonstrate that the NPs induce autophagy in M. tuberculosis-infectedmacrophages. Treatment of H37Rv infected C57BL/6 mice with these NPs reduced M. tuberculosis burden in the lungs of mice andmodulated cytokines and chemokines and this work demonstrates that these immunomodulatory NPs are a potential treatmentapproach for TB

Description

Keywords

Mycobacterium tuberculosis, Immunotherapy, Host-directed therapy, Autophagy induction, Innate immunity

Citation

Bekale, R.B., Maphasa, R.E., D’Souza, S., Hsu, N.J., Walters, A., Okugbeni, N., Kinnear, C., Jacobs, M., Sampson, S.L., Meyer, M. and Morse, G.D., 2025. Immunomodulatory Nanoparticles Induce Autophagy in Macrophages and Reduce Mycobacterium tuberculosis Burden in the Lungs of Mice. ACS Infectious Diseases.