| First Author | Rappe JCF | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 11 | PubMed ID | 34473195 |
| Mgi Jnum | J:317308 | Mgi Id | MGI:6790110 |
| Doi | 10.1084/jem.20201631 | Citation | Rappe JCF, et al. (2021) A TLR7 antagonist restricts interferon-dependent and -independent immunopathology in a mouse model of severe influenza. J Exp Med 218(11) |
| abstractText | 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. |
