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Brain immune cells ...
Brain immune cells undergo cGAS-STING-dependent apoptosis during herpes simplex virus type 1 infection.
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Reinert, Line S (author)
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Rashidi, Ahmad S (author)
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Tran, Diana N (author)
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Katzilieris-Petras, Georgios (author)
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Hvidt, Astrid K (author)
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Gohr, Mette (author)
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- Fruhwürth, Stefanie, 1987 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Bodda, Chiranjeevi (author)
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Thomsen, Martin K (author)
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Vendelbo, Mikkel H (author)
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Khan, Ahmad Raza (author)
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Hansen, Brian (author)
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- Bergström, Petra (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Agholme, Lotta (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Mogensen, Trine H (author)
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Christensen, Maria H (author)
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Nyengaard, Jens R (author)
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Sen, Ganes C (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Verjans, Georges Mgm (author)
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Paluden, Soren R (author)
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(creator_code:org_t)
- 2020
- 2020
- English.
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In: The Journal of clinical investigation. - 1558-8238. ; 131:1
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Protection of the brain from viral infections involves the type I interferon (IFN-I) system, defects in which renders humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels leads to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we here show that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, while lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices, or mice treated with caspase inhibitor, exhibited lower viral load and improved outcome of infection. Collectively, we identify an activation-induced apoptosis program in brain immune cells which down-modulates local immune responses.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Reinert, Line S
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Rashidi, Ahmad S
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Tran, Diana N
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Katzilieris-Petr ...
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Hvidt, Astrid K
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Gohr, Mette
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show more...
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Fruhwürth, Stefa ...
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Bodda, Chiranjee ...
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Thomsen, Martin ...
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Vendelbo, Mikkel ...
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Khan, Ahmad Raza
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Hansen, Brian
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Bergström, Petra
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Agholme, Lotta
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Mogensen, Trine ...
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Christensen, Mar ...
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Nyengaard, Jens ...
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Sen, Ganes C
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Zetterberg, Henr ...
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Verjans, Georges ...
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Paluden, Soren R
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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The Journal of c ...
- By the university
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University of Gothenburg