Cited 40 times in
SARS-CoV-2 Infection of Microglia Elicits Proinflammatory Activation and Apoptotic Cell Death
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이준용 | - |
dc.date.accessioned | 2022-12-22T02:28:43Z | - |
dc.date.available | 2022-12-22T02:28:43Z | - |
dc.date.issued | 2022-06 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/191598 | - |
dc.description.abstract | Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes various neurological symptoms in patients with coronavirus disease 2019 (COVID-19). The most dominant immune cells in the brain are microglia. Yet, the relationship between neurological manifestations, neuroinflammation, and host immune response of microglia to SARS-CoV-2 has not been well characterized. Here, we reported that SARS-CoV-2 can directly infect human microglia, eliciting M1-like proinflammatory responses, followed by cytopathic effects. Specifically, SARS-CoV-2 infected human microglial clone 3 (HMC3), leading to inflammatory activation and cell death. RNA sequencing (RNA-seq) analysis also revealed that endoplasmic reticulum (ER) stress and immune responses were induced in the early, and apoptotic processes in the late phases of viral infection. SARS-CoV-2-infected HMC3 showed the M1 phenotype and produced proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α), but not the anti-inflammatory cytokine IL-10. After this proinflammatory activation, SARS-CoV-2 infection promoted both intrinsic and extrinsic death receptor-mediated apoptosis in HMC3. Using K18-hACE2 transgenic mice, murine microglia were also infected by intranasal inoculation of SARS-CoV-2. This infection induced the acute production of proinflammatory microglial IL-6 and TNF-α and provoked a chronic loss of microglia. Our findings suggest that microglia are potential mediators of SARS-CoV-2-induced neurological problems and, consequently, can be targets of therapeutic strategies against neurological diseases in patients with COVID-19. IMPORTANCE Recent studies reported neurological and cognitive sequelae in patients with COVID-19 months after the viral infection with several symptoms, including ageusia, anosmia, asthenia, headache, and brain fog. Our conclusions raise awareness of COVID-19-related microglia-mediated neurological disorders to develop treatment strategies for the affected patients. We also indicated that HMC3 was a novel human cell line susceptible to SARS-CoV-2 infection that exhibited cytopathic effects, which could be further used to investigate cellular and molecular mechanisms of neurological manifestations of patients with COVID-19. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | ASM Press | - |
dc.relation.isPartOf | MICROBIOLOGY SPECTRUM | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Apoptosis* | - |
dc.subject.MESH | COVID-19* | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Cytokines / metabolism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Interleukin-6 | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Transgenic | - |
dc.subject.MESH | Microglia* / virology | - |
dc.subject.MESH | SARS-CoV-2 | - |
dc.subject.MESH | Tumor Necrosis Factor-alpha | - |
dc.title | SARS-CoV-2 Infection of Microglia Elicits Proinflammatory Activation and Apoptotic Cell Death | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Microbiology (미생물학교실) | - |
dc.contributor.googleauthor | Gi Uk Jeong | - |
dc.contributor.googleauthor | Jaemyun Lyu | - |
dc.contributor.googleauthor | Kyun-Do Kim | - |
dc.contributor.googleauthor | Young Cheul Chung | - |
dc.contributor.googleauthor | Gun Young Yoon | - |
dc.contributor.googleauthor | Sumin Lee | - |
dc.contributor.googleauthor | Insu Hwang | - |
dc.contributor.googleauthor | Won-Ho Shin | - |
dc.contributor.googleauthor | Junsu Ko | - |
dc.contributor.googleauthor | June-Yong Lee | - |
dc.contributor.googleauthor | Young-Chan Kwon | - |
dc.identifier.doi | 10.1128/spectrum.01091-22 | - |
dc.contributor.localId | A06330 | - |
dc.relation.journalcode | J04082 | - |
dc.identifier.eissn | 2165-0497 | - |
dc.identifier.pmid | 35510852 | - |
dc.subject.keyword | M1 polarization | - |
dc.subject.keyword | SARS-CoV-2 | - |
dc.subject.keyword | apoptosis | - |
dc.subject.keyword | microglia | - |
dc.subject.keyword | neuroinflammation | - |
dc.contributor.alternativeName | Lee, June-Yong | - |
dc.contributor.affiliatedAuthor | 이준용 | - |
dc.citation.volume | 10 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | e0109122 | - |
dc.identifier.bibliographicCitation | MICROBIOLOGY SPECTRUM, Vol.10(3) : e0109122, 2022-06 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.