Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease
Human Borna disease virus 1 (BoDV-1) encephalitis is a severe emerging disease with a very high case-fatality rate. While the clinical disease, case definitions, diagnostic algorithms and neuropathology have been described, very little is known about the immunological processes of human BoDV-1 encep...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2022.2098831 |
| _version_ | 1811312303351529472 |
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| author | Jessica Rauch Johanna Friederike Steffen Birgit Muntau Jana Gisbrecht Kirsten Pörtner Christiane Herden Hans Helmut Niller Markus Bauswein Dennis Rubbenstroth Ute Mehlhoop Petra Allartz Dennis Tappe |
| author_facet | Jessica Rauch Johanna Friederike Steffen Birgit Muntau Jana Gisbrecht Kirsten Pörtner Christiane Herden Hans Helmut Niller Markus Bauswein Dennis Rubbenstroth Ute Mehlhoop Petra Allartz Dennis Tappe |
| author_sort | Jessica Rauch |
| collection | DOAJ |
| description | Human Borna disease virus 1 (BoDV-1) encephalitis is a severe emerging disease with a very high case-fatality rate. While the clinical disease, case definitions, diagnostic algorithms and neuropathology have been described, very little is known about the immunological processes of human BoDV-1 encephalitis. Here, we analyzed serum and cerebrospinal fluid (CSF) samples from 10 patients with fatal BoDV-1 encephalitis for changes of different cytokines, chemokines, growth factors and other biomarkers over time. From one of these individuals, also autoptic formalin-fixed brain tissue was analyzed for the expression of inflammatory biomarkers by mRNA levels and immunostaining; in a further patient, only formalin-fixed brain tissue was available and examined in addition. A marked and increasing immune activation from the initial phase to the last phase of acute BoDV-1 encephalitis is shown in serum and CSF, characterized by cytokine concentration changes (IFNγ, IL-5, IL-6, IL-9, IL-10, IL-12p40, IL-13, IL-18, TGF-β1) with a predominantly pro-inflammatory pattern over time. IFNγ production was demonstrated in endothelial cells, astrocytes and microglia, IL-6 in activated microglia, and TGF-β1 in endothelial cells, activated astrocytes and microglia. This was paralleled by an increase of chemokines (CCL-2, CCL-5, CXCL-10, IL-8) to attract immune cells to the site of infection, contributing to inflammation and tissue damage. Pathologically low growth factor levels (BDNF, β-NGF, PDGF) were seen. Changed levels of arginase and sTREM further fostered the pro-inflammatory state. This dysbalanced, pro-inflammatory state likely contributes importantly to the fatal outcome of human BoDV-1 encephalitis, and might be a key target for possible treatment attempts. |
| first_indexed | 2024-04-13T10:34:50Z |
| format | Article |
| id | doaj.art-824c0ef4b2894095bef1408f73261424 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-13T10:34:50Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-824c0ef4b2894095bef1408f732614242022-12-22T02:50:05ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512022-12-011111843185610.1080/22221751.2022.2098831Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of diseaseJessica Rauch0Johanna Friederike Steffen1Birgit Muntau2Jana Gisbrecht3Kirsten Pörtner4Christiane Herden5Hans Helmut Niller6Markus Bauswein7Dennis Rubbenstroth8Ute Mehlhoop9Petra Allartz10Dennis Tappe11Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyBernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyBernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyBernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyDepartment of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, GermanyInstitute for Veterinary Pathology, Justus-Liebig-University Gießen, Gießen, GermanyInstitute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, GermanyInstitute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, GermanyFriedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, GermanyBernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyBernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyBernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyHuman Borna disease virus 1 (BoDV-1) encephalitis is a severe emerging disease with a very high case-fatality rate. While the clinical disease, case definitions, diagnostic algorithms and neuropathology have been described, very little is known about the immunological processes of human BoDV-1 encephalitis. Here, we analyzed serum and cerebrospinal fluid (CSF) samples from 10 patients with fatal BoDV-1 encephalitis for changes of different cytokines, chemokines, growth factors and other biomarkers over time. From one of these individuals, also autoptic formalin-fixed brain tissue was analyzed for the expression of inflammatory biomarkers by mRNA levels and immunostaining; in a further patient, only formalin-fixed brain tissue was available and examined in addition. A marked and increasing immune activation from the initial phase to the last phase of acute BoDV-1 encephalitis is shown in serum and CSF, characterized by cytokine concentration changes (IFNγ, IL-5, IL-6, IL-9, IL-10, IL-12p40, IL-13, IL-18, TGF-β1) with a predominantly pro-inflammatory pattern over time. IFNγ production was demonstrated in endothelial cells, astrocytes and microglia, IL-6 in activated microglia, and TGF-β1 in endothelial cells, activated astrocytes and microglia. This was paralleled by an increase of chemokines (CCL-2, CCL-5, CXCL-10, IL-8) to attract immune cells to the site of infection, contributing to inflammation and tissue damage. Pathologically low growth factor levels (BDNF, β-NGF, PDGF) were seen. Changed levels of arginase and sTREM further fostered the pro-inflammatory state. This dysbalanced, pro-inflammatory state likely contributes importantly to the fatal outcome of human BoDV-1 encephalitis, and might be a key target for possible treatment attempts.https://www.tandfonline.com/doi/10.1080/22221751.2022.2098831BoDV-1bornavirusmicrogliaastrocytecytokinechemokine |
| spellingShingle | Jessica Rauch Johanna Friederike Steffen Birgit Muntau Jana Gisbrecht Kirsten Pörtner Christiane Herden Hans Helmut Niller Markus Bauswein Dennis Rubbenstroth Ute Mehlhoop Petra Allartz Dennis Tappe Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease Emerging Microbes and Infections BoDV-1 bornavirus microglia astrocyte cytokine chemokine |
| title | Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease |
| title_full | Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease |
| title_fullStr | Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease |
| title_full_unstemmed | Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease |
| title_short | Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease |
| title_sort | human borna disease virus 1 encephalitis shows marked pro inflammatory biomarker and tissue immunoactivation during the course of disease |
| topic | BoDV-1 bornavirus microglia astrocyte cytokine chemokine |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2022.2098831 |
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