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 Mycobacterium 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 the investigation of novel approaches for the treatment of TB. Here, we report a host-directed approach, employing biomimetic Curdlan poly(lactic-co-glycolic acid) (C-PLGA) nanoparticles (NPs), and examine autophagy induction in infected macrophages, eradication of M. tuberculosis and immune modulation in a mouse model. We demonstrate that the NPs induce autophagy in M. tuberculosis-infected macrophages. Treatment of H37Rv infected C57BL/6 mice with these NPs reduced M. tuberculosis burden 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.
[1]Univ Western Cape, Sch Pharm, Infect Dis Nanomed Res Grp, ZA-7535 Cape Town, South Africa.
[2]Univ Cape Town, Dept Pathol, Div Immunol, ZA-7701 Cape Town, South Africa.
[3]Natl Hlth Lab Serv, ZA-8005 Cape Town, South Africa.
[4]Univ Cape Town, Neurosci Inst, ZA-7925 Cape Town, South Africa.
[5]Univ Cape Town, Inst Infect Dis & Mol Med, Fac Hlth Sci, ZA-7925 Cape Town, South Africa.
[6]Stellenbosch Univ, Fac Med & Hlth Sci, NRF Ctr Excellence Biomed TB Res, South African Med Res Council Ctr TB Res,DSI,Div M, ZA-7505 Cape Town, South Africa.
[7]South African Med Res Council Genom Platform, ZA-7501 Cape Town, South Africa.
[8]Univ Western Cape, Mintek Nanotechnol Innovat Ctr, Dept Sci & Innovat, Dept Biotechnol,Biolabels Node, ZA-7535 Cape Town, South Africa.
[9]SUNY Buffalo, Ctr Integrated Global Biomed Sci, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14215 USA.
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