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Article

Immunoregulatory and Antimicrobial Activity of Bovine Neutrophil β-Defensin-5-Loaded PLGA Nanoparticles against Mycobacterium bovis

1
Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
2
Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(12), 1172; https://doi.org/10.3390/pharmaceutics12121172
Received: 6 November 2020 / Revised: 26 November 2020 / Accepted: 27 November 2020 / Published: 1 December 2020
Mycobacterium bovis (M. bovis) is a member of the Mycobacterium tuberculosis complex imposing a high zoonotic threat to human health. The limited efficacy of BCG (Bacillus Calmette–Guérin) and upsurges of drug-resistant tuberculosis require new effective vaccination approaches and anti-TB drugs. Poly (lactic-co-glycolic acid) (PLGA) is a preferential drug delivery system candidate. In this study, we formulated PLGA nanoparticles (NPs) encapsulating the recombinant protein bovine neutrophil β-defensin-5 (B5), and investigated its role in immunomodulation and antimicrobial activity against M. bovis challenge. Using the classical water–oil–water solvent-evaporation method, B5-NPs were prepared, with encapsulation efficiency of 85.5% ± 2.5%. These spherical NPs were 206.6 ± 26.6 nm in diameter, with a negatively charged surface (ζ-potential −27.1 ± 1.5 mV). The encapsulated B5 protein from B5-NPs was released slowly under physiological conditions. B5 or B5-NPs efficiently enhanced the secretion of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-10 in J774A.1 macrophages. B5-NPs-immunized mice showed significant increases in the production of TNF-α and immunoglobulin A (IgA) in serum, and the proportion of CD4+ T cells in spleen compared with B5 alone. In immunoprotection studies, B5-NPs-immunized mice displayed significant reductions in pulmonary inflammatory area, bacterial burden in the lungs and spleen at 4-week after M. bovis challenge. In treatment studies, B5, but not B5-NPs, assisted rifampicin (RIF) with inhibition of bacterial replication in the lungs and spleen. Moreover, B5 alone also significantly reduced the bacterial load in the lungs and spleen. Altogether, our findings highlight the significance of the B5-PLGA NPs in terms of promoting the immune effect of BCG and the B5 in enhancing the therapeutic effect of RIF against M. bovis. View Full-Text
Keywords: PLGA; nanoparticles; bovine neutrophil β-defensin-5; Mycobacterium bovis; immunoregulation; antimicrobial activity PLGA; nanoparticles; bovine neutrophil β-defensin-5; Mycobacterium bovis; immunoregulation; antimicrobial activity
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MDPI and ACS Style

Liang, Z.; Liu, Y.; Sun, X.; Lin, J.; Yao, J.; Song, Y.; Li, M.; Liu, T.; Zhou, X. Immunoregulatory and Antimicrobial Activity of Bovine Neutrophil β-Defensin-5-Loaded PLGA Nanoparticles against Mycobacterium bovis. Pharmaceutics 2020, 12, 1172. https://doi.org/10.3390/pharmaceutics12121172

AMA Style

Liang Z, Liu Y, Sun X, Lin J, Yao J, Song Y, Li M, Liu T, Zhou X. Immunoregulatory and Antimicrobial Activity of Bovine Neutrophil β-Defensin-5-Loaded PLGA Nanoparticles against Mycobacterium bovis. Pharmaceutics. 2020; 12(12):1172. https://doi.org/10.3390/pharmaceutics12121172

Chicago/Turabian Style

Liang, Zhengmin, Yiduo Liu, Xingya Sun, Jingjun Lin, Jiao Yao, Yinjuan Song, Miaoxuan Li, Tianlong Liu, and Xiangmei Zhou. 2020. "Immunoregulatory and Antimicrobial Activity of Bovine Neutrophil β-Defensin-5-Loaded PLGA Nanoparticles against Mycobacterium bovis" Pharmaceutics 12, no. 12: 1172. https://doi.org/10.3390/pharmaceutics12121172

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