Rappe, Julie C. F. and Finsterbusch, Katja and Crotta, Stefania and Mack, Matthias and Priestnall, Simon L. and Wack, Andreas (2021) A TLR7 antagonist restricts interferon-dependent and -independent immunopathology in a mouse model of severe influenza. JOURNAL OF EXPERIMENTAL MEDICINE, 218 (11): e20201631. ISSN 0022-1007, 1540-9538
Full text not available from this repository. (Request a copy)Abstract
Cytokine-mediated immune-cell recruitment and inflammation contribute to protection in respiratory virus infection. However, uncontrolled inflammation and the "cytokine storm" are hallmarks of immunopathology in severe infection. Cytokine storm is a broad term for a phenomenon with diverse characteristics and drivers, depending on host genetics, age, and other factors. Taking advantage of the differential use of virus-sensing systems by different cell types, we test the hypothesis that specifically blocking TLR7-dependent, immune cell-produced cytokines reduces influenza-related immunopathology. In a mouse model of severe influenza characterized by a type I interferon (IFN-I)-driven cytokine storm, TLR7 antagonist treatment leaves epithelial antiviral responses unaltered but acts through pDCs and monocytes to reduce IFN-I and other cytokines in the lung, thus ameliorating inflammation and severity. Moreover, even in the absence of IFN-I signaling, TLR7 antagonism reduces inflammation and mortality driven by monocyte-produced chemoattractants and neutrophil recruitment into the infected lung. Hence, TLR7 antagonism reduces diverse types of cytokine storm in severe influenza.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLASMACYTOID DENDRITIC CELLS; DEMONSTRATES CLINICAL ACTIVITY; SINGLE-STRANDED RNA; I INTERFERON; LUNG INJURY; RECEPTOR 7; AIRWAY INFLAMMATION; MURINE MODEL; PHASE 2A; RECOGNITION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Sep 2022 07:29 |
| Last Modified: | 12 Sep 2022 07:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47163 |
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