AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

Manganese nanodepot augments host immune response against coronavirus

Yizhe Sun1, Yue Yin1, Lidong Gong1, Zichao Liang1, Chuanda Zhu1, Caixia Ren2, Nan Zheng3, Qiang Zhang4, Haibin Liu5, Wei Liu5, Fuping You1, Dan Lu1( ), Zhiqiang Lin1( )
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China
Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), National Drug Clinical Trial Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Department of General Surgery, Xinjiang Production and Construction Corps Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830002, China
Show Author Information

Graphical Abstract

Abstract

Interferon (IFN) responses are central to host defense against coronavirus and other virus infections. Manganese (Mn) is capable of inducing IFN production, but its applications are limited by nonspecific distributions and neurotoxicity. Here, we exploit chemical engineering strategy to fabricate a nanodepot of manganese (nanoMn) based on Mn2+. Compared with free Mn2+, nanoMn enhances cellular uptake and persistent release of Mn2+ in a pH-sensitive manner, thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo. Preferentially phagocytosed by macrophages, nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci, eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage. Besides, nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation, suggesting its potential as a vaccine adjuvant. Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese. Therefore, nanoMn offers a simple, safe, and robust nanoparticle-based strategy against coronavirus.

Keywords

interferoncoronavirusmanganese nanodepot (nanoMn)macrophage polarizationvaccine adjuvant

Electronic Supplementary Material

Download File(s)
12274_2020_3243_MOESM1_ESM.pdf (2.9 MB)

References

[1]
W. J. Guan,; W. H. Liang,; Y. Zhao,; H. R. Liang,; Z. S. Chen,; Y. M. Li,; X. Q. Liu,; R. C. Chen,; C. L. Tang,; T. Wang, et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: A nationwide analysis. Eur. Respir. J. 2020, 55, 2000547.
Crossref Google Scholar
[2]
W. J. Guan,; Z. Y. Ni,; Y. Hu,; W. H. Liang,; C. Q. Ou,; J. X. He,; L. Liu,; H. Shan,; C. L. Lei,; D. S. C. Hui, et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020, 382, 1708-1720.
Crossref Google Scholar
[3]
G. D. Li,; E. De Clercq, Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov. 2020, 19, 149-150.
Crossref Google Scholar
[4]
M. Pal,; G. Berhanu,; C. Desalegn,; V. Kandi, Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): An update. Cureus 2020, 12, e7423.
Crossref Google Scholar
[5]
L. Bao,; W. Deng,; B. Y. Huang,; H. Gao,; J. N. Liu,; L. L. Ren,; Q. Wei,; P. Yu,; Y. F. Xu,; F. F. Qi, et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 2020, 583, 830-833.
Crossref Google Scholar
[6]
R. L. Graham,; E. F. Donaldson,; R. S. Baric, A decade after SARS: Strategies for controlling emerging coronaviruses. Nat. Rev. Microbiol. 2013, 11, 836-848.
Crossref Google Scholar
[7]
K. D. Kim,; J. Zhao,; S. Auh,; X. M. Yang,; P. S. Du,; H. Tang,; Y. X. Fu, Adaptive immune cells temper initial innate responses. Nat. Med. 2007, 13, 1248-1252.
Crossref Google Scholar
[8]
Z. S. Yang,; J. Du,; G. Chen,; J. Zhao,; X. M. Yang,; L. S. Su,; G. H. Cheng,; H. Tang, Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice. Virol. Sin. 2014, 29, 393-402.
Crossref Google Scholar
[9]
S. Q. Ma,; J. Zhang,; Y. S. Wang,; J. Xia,; P. Liu,; H. Luo,; M. Y. Wang, Glucocorticoid therapy delays the clearance of SARS-CoV-2 RNA in an asymptomatic COVID-19 patient. J. Med. Virol. 2020, 92, 2396-2397.
Crossref Google Scholar
[10]
S. Shalhoub, Interferon beta-1b for COVID-19. Lancet 2020, 395, 1670-1671.
Crossref Google Scholar
[11]
G. Antonelli,; O. Turriziani,; A. Pierangeli,; G. d'Ettorre,; G. Galardo,; F. Pugliese,; C. M. Mastroianni,; C. Scagnolari, Type I interferons can be detected in respiratory swabs from SARS-Cov-2 infected patients. J. Clin. Virol. 2020, 128, 104450.
Crossref Google Scholar
[12]
M. Haji Abdolvahab,; M. R. K. Mofrad,; H. Schellekens, Chapter eight - interferon beta: From molecular level to therapeutic effects. Int. Rev. Cell Mol. Biol. 2016, 326, 343-372.
Crossref Google Scholar
[13]
H. Kumar,; T. Kawai,; S. Akira, Pathogen recognition by the innate immune system. Int. Rev. Immunol. 2011, 30, 16-34.
Crossref Google Scholar
[14]
C. G. Wang,; Y. K. Guan,; M. Z. Lv,; R. Zhang,; Z. Y. Guo,; X. M. Wei,; X. M. Du,; J. Yang,; T. Li,; Y. Wan, et al. Manganese increases the sensitivity of the cGAS-STING pathway for double-stranded DNA and is required for the host defense against DNA viruses. Immunity 2018, 48, 675-687.e7.
Crossref Google Scholar
[15]
T. V. Peres,; M. R. C. Schettinger,; P. Chen,; F. Carvalho,; D. S. Avila,; A. B. Bowman,; M. Aschner, “Manganese-induced neurotoxicity: A review of its behavioral consequences and neuroprotective strategies”. BMC Pharmacol. Toxicol. 2016, 17, 57.
Crossref Google Scholar
[16]
R. B. Tjalkens,; K. A. Popichak,; K. A. Kirkley, Inflammatory activation of microglia and astrocytes in manganese neurotoxicity. In Neurotoxicity of Metals; M. Aschner,; L. G. Costa,, Eds.; Springer: Cham, 2017; pp 159-181.
Crossref
[17]
A. L. Blasius,; B. Beutler, Intracellular toll-like receptors. Immunity 2010, 32, 305-315.
Crossref Google Scholar
[18]
X. Y. Miao,; X. F. Leng,; Q. Zhang, The current state of nanoparticle-induced macrophage polarization and reprogramming research. Int. J. Mol. Sci. 2017, 18, 336.
Crossref Google Scholar
[19]
T. R. O’Brien,; D. L. Thomas,; S. S. Jackson,; L. Prokunina-Olsson,; R. P. Donnelly,; R. Hartmann, Weak induction of interferon expression by severe acute respiratory syndrome coronavirus 2 supports clinical trials of interferon-λ to treat early coronavirus disease 2019. Clin. Infect. Dis. 2020, 71, 1410-1412.
Crossref Google Scholar
[20]
F. McNab,; K. Mayer-Barber,; A. Sher,; A. Wack,; A. O'Garra, Type I interferons in infectious disease. Nat. Rev. Immunol. 2015, 15, 87-103.
Crossref Google Scholar
[21]
A. S. Poltavets,; P. A. Vishnyakova,; A. V. Elchaninov,; G. T. Sukhikh,; T. K. Fatkhudinov, Macrophage modification strategies for efficient cell therapy. Cells 2020, 9, 1535.
Crossref Google Scholar
[22]
H. J. Yu,; Y. L. Zou,; Y. G. Wang,; X. N. Huang,; G. Huang,; B. D. Sumer,; D. A. Boothman,; J. M. Gao, Overcoming endosomal barrier by amphotericin B-loaded dual pH-responsive PDMA-b-PDPA micelleplexes for siRNA delivery. ACS Nano 2011, 5, 9246-9255.
Crossref Google Scholar
[23]
S. A. Smith,; L. I. Selby,; A. P. R. Johnston,; G. K. Such, The endosomal escape of nanoparticles: Toward more efficient cellular delivery. Bioconjugate Chem. 2019, 30, 263-272.
Crossref Google Scholar
[24]
W. Lin,; D. R. Vann,; P. T. Doulias,; T. Wang,; G. Landesberg,; X. L. Li,; E. Ricciotti,; R. Scalia,; M. He,; N. J. Hand, et al. Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. J. Clin. Invest. 2017, 127, 2407-2417.
Crossref Google Scholar
[25]
K. J. Horning,; S. W. Caito,; K. G. Tipps,; A. B. Bowman,; M. Aschner, Manganese is essential for neuronal health. Annu. Rev. Nutr. 2015, 35, 71-108.
Crossref Google Scholar
[26]
F. Ginhoux,; S. Jung, Monocytes and macrophages: Developmental pathways and tissue homeostasis. Nat. Rev. Immunol. 2014, 14, 392-404.
Crossref Google Scholar
[27]
C. Shi,; E. G. Pamer, Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol. 2011, 11, 762-774.
Crossref Google Scholar
[28]
M. Catanzaro,; F. Fagiani,; M. Racchi,; E. Corsini,; S. Govoni,; C. Lanni, Immune response in COVID-19: Addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal. Transduct. Target. Ther. 2020, 5, 84.
Crossref Google Scholar
[29]
F. Stauffer,; T. El-Bacha,; A. Da Poian, Advances in the development of inactivated virus vaccines. Recent Patents Anti-Infect. Drug Discov. 2006, 1, 291-296.
Crossref Google Scholar
[30]
S. G. Reed,; M. T. Orr,; C. B. Fox, Key roles of adjuvants in modern vaccines. Nat. Med. 2013, 19, 1597-1608.
Crossref Google Scholar
[31]
R. H. Griesenauer,; M. S. Kinch, An overview of FDA-approved vaccines & their innovators. Expert Rev. Vaccines 2017, 16, 1253-1266.
Crossref Google Scholar
[32]
H. HogenEsch,; D. T. O'Hagan,; C. B. Fox, Optimizing the utilization of aluminum adjuvants in vaccines: You might just get what you want. NPJ Vaccines 2018, 3, 51.
Crossref Google Scholar
[33]
J. R. Mascola,; A. S. Fauci, Novel vaccine technologies for the 21st century. Nat. Rev. Immunol. 2020, 20, 87-88.
Crossref Google Scholar
[34]
X. Li,; X. P. Wang,; A. Ito, Tailoring inorganic nanoadjuvants towards next-generation vaccines. Chem. Soc. Rev. 2018, 47, 4954-4980.
Crossref Google Scholar
[35]
J. O. G. Karlsson,; L. J. Ignarro,; I. Lundström,; P. Jynge,; T. Almén, Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties. Drug Discov. Today 2015, 20, 411-421.
Crossref Google Scholar
[36]
M. Z. Lv,; M. X. Chen,; R. Zhang,; W. Zhang,; C. G. Wang,; Y. Zhang,; X. M. Wei,; Y. K. Guan,; J. J. Liu,; K. C. Feng, et al. Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy. Cell Res. 2020, 30, 966-979.
Crossref Google Scholar
Nano Research
Volume 14 Issue 5,
May 2021
Pages 1260-1272
DOI: 10.1007/s12274-020-3243-5
Cite this article:
Sun Y, Yin Y, Gong L, et al. Manganese nanodepot augments host immune response against coronavirus. Nano Research, 2021, 14(5): 1260-1272. https://doi.org/10.1007/s12274-020-3243-5
Topics:
MacrophagesManganeseMetal nanoparticlesViruses

893

Views

32

Crossref

N/A

Web of Science

31

Scopus

2

CSCD

Altmetrics
Received: 16 September 2020
Revised: 03 November 2020
Accepted: 14 November 2020
Published: 29 December 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature
Return