NK Cell Activation in Human Hantavirus Infection Explained by Virus-Induced IL-15/IL15Rα Expression

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Hantaviruses cause severe clinical infections with up to 50% case-fatality rates. The diseases represent an important global health problem as no vaccine or specific treatment is available. The most prominent hallmark in patients is strong immune activation, reflected as massive CD8 T and NK cell expansion, accompanied by severe vascular leakage. The mechanisms behind this massive immune activation are still not fully understood. Here, we first assessed the expression of several activation markers and receptors on NK cells derived from hantavirus-infected patients using flow cytometry. High NK cell activation was observed during the acute phase of clinical infection. To address possible underlying mechanisms explaining this NK cell activation, we established an in vitro hantavirus infection model using human primary endothelial cells, the natural in vivo targets of the virus. We demonstrate hantavirus-induced IL-15/IL-15Rα on infected endothelial cells, and show that this results in NK cell activation, similar to the profile found in hantavirus-infected patients. Interestingly, these activated NK cells were able to kill uninfected endothelial cells despite their normal expression of HLA class I. The present data add further insights into hantavirus-induced pathogenesis and suggest possible targets for future therapeutical interventions in these severe diseases.

Vyšlo v časopise: NK Cell Activation in Human Hantavirus Infection Explained by Virus-Induced IL-15/IL15Rα Expression. PLoS Pathog 10(11): e32767. doi:10.1371/journal.ppat.1004521
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004521

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