EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 production Article Swipe
Zhen Luo
,
Rui Su
,
Wenbiao Wang
,
Yicong Liang
,
Xiaofeng Zeng
,
Muhammad Adnan Shereen
,
Nadia Bashir
,
Qi Zhang
,
Ling Zhao
,
Kailang Wu
,
Yingle Liu
,
Jianguo Wu
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1371/journal.ppat.1008142
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1371/journal.ppat.1008142
As a neurotropic virus, human Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease (HFMD) and may develop severe neurological disorders in infants. Toll-like receptor 7 (TLR7) acts as an innate immune receptor and is also a death receptor in the central nervous system (CNS). However, the mechanisms underlying the regulation of TLR7-mediated brain pathogenesis upon EV71 infection remain largely elusive. Here we reveal a novel mechanism by which EV71 infects astrocytes in the brain and induces neural pathogenesis via TLR7 and interleukin-6 (IL-6) in C57BL/6 mice and in human astroglioma U251 cells. Upon EV71 infection, wild-type (WT) mice displayed more significant body weight loss, higher clinical scores, and lower survival rates as compared with TLR7-/- mice. In the cerebral cortex of EV71-infected mice, neurofilament integrity was disrupted, and inflammatory cell infiltration and neurodegeneration were induced in WT mice, whereas these were largely absent in TLR7-/- mice. Similarly, IL-6 production, Caspase-3 cleavage, and cell apoptosis were significantly higher in EV71-infected WT mice as compared with TLR7-/- mice. Moreover, EV71 preferentially infected and induced IL-6 in astrocytes of mice brain. In U251 cells, EV71-induced IL-6 production and cell apoptosis were suppressed by shRNA-mediated knockdown of TLR7 (shTLR7). Moreover, in the cerebral cortex of EV71-infected mice, the blockade of IL-6 with anti-IL-6 antibody (IL-6-Ab) restored the body weight loss, attenuated clinical scores, improved survival rates, reduced the disruption of neurofilament integrity, decreased cell apoptotic induction, and lowered levels of Caspase-3 cleavage. Similarly, in EV71-infected U251 cells, IL-6-Ab blocked EV71-induced IL-6 production and cell apoptosis in response to viral infection. Collectively, it's exhibited TLR7 upregulation, IL-6 induction and astrocytic cell apoptosis in EV71-infected human brain. Taken together, we propose that EV71 infects astrocytes of the cerebral cortex in mice and human and triggers TLR7 signaling and IL-6 release, subsequently inducing neural pathogenesis in the brain.
Related Topics
Concepts
Neurodegeneration
TLR7
Neuroscience
Cell biology
Biology
Medicine
Immunology
Toll-like receptor
Immune system
Innate immune system
Disease
Internal medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.ppat.1008142
- https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1008142&type=printable
- OA Status
- gold
- Cited By
- 96
- References
- 57
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2985864163
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2985864163Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.ppat.1008142Digital Object Identifier
- Title
-
EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 productionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-11-15Full publication date if available
- Authors
-
Zhen Luo, Rui Su, Wenbiao Wang, Yicong Liang, Xiaofeng Zeng, Muhammad Adnan Shereen, Nadia Bashir, Qi Zhang, Ling Zhao, Kailang Wu, Yingle Liu, Jianguo WuList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.ppat.1008142Publisher landing page
- PDF URL
-
https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1008142&type=printableDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1008142&type=printableDirect OA link when available
- Concepts
-
Neurodegeneration, TLR7, Neuroscience, Cell biology, Biology, Medicine, Immunology, Toll-like receptor, Immune system, Innate immune system, Disease, Internal medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
96Total citation count in OpenAlex
- Citations by year (recent)
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2025: 19, 2024: 18, 2023: 20, 2022: 13, 2021: 15Per-year citation counts (last 5 years)
- References (count)
-
57Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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