Immunomodulatory Nanoparticles Induce Autophagy in Macrophages and ReduceBurden in the Lungs of Mice.

Abstract

Tuberculosis (TB) is the leading cause of death from infectious disease. Macrophages are the primary immune responders and become the primary host cells for the causative agent. Following the uptake of, the inherent antimicrobial action of macrophages is dampened, enabling the bacterium to reside within these cells and multiply. Rising resistance ofto antibiotics has led to the investigation of novel approaches for the treatment of TB. Here, we report a host-directed approach, employing biomimetic Curdlan poly(lactic--glycolic acid) (C-PLGA) nanoparticles (NPs), and examine autophagy induction in infected macrophages, eradication ofand immune modulation in a mouse model. We demonstrate that the NPs induce autophagy in-infected macrophages. Treatment of H37Rv infected C57BL/6 mice with these NPs reducedburden in the lungs of mice and modulated cytokines and chemokines and this work demonstrates that these immunomodulatory NPs are a potential treatment approach for TB.