Rauch, Jessica and Steffen, Johanna Friederike and Muntau, Birgit and Gisbrecht, Jana and Poertner, Kirsten and Herden, Christiane and Niller, Hans Helmut and Bauswein, Markus and Rubbenstroth, Dennis and Mehlhoop, Ute and Allartz, Petra and Tappe, Dennis (2022) Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease. EMERGING MICROBES & INFECTIONS, 11 (1). pp. 1843-1856. ISSN , 2222-1751
Full text not available from this repository. (Request a copy)Abstract
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 (IFN gamma, IL-5, IL-6, IL-9, IL-10, IL-12p40, IL-13, IL-18, TGF-beta 1) with a predominantly pro-inflammatory pattern over time. IFN gamma production was demonstrated in endothelial cells, astrocytes and microglia, IL-6 in activated microglia, and TGF-beta 1 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, beta-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELLS; ACTIVATED ASTROCYTES; CEREBROSPINAL-FLUID; PATHOGENESIS; INFECTION; NEURONS; GERMANY; BRAIN; MODEL; BoDV-1; bornavirus; microglia; astrocyte; cytokine; chemokine |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Feb 2024 10:44 |
| Last Modified: | 27 Feb 2024 10:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57955 |
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