Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 11, Iss 1, Pp 1843-1856 (2022)
Druh dokumentu: article
ISSN: 22221751
2222-1751
73261424
DOI: 10.1080/22221751.2022.2098831
Popis: 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.
Databáze: Directory of Open Access Journals
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