| First Author | Webster B | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 29914621 | Mgi Jnum | J:264199 |
| Mgi Id | MGI:6191838 | Doi | 10.7554/eLife.34273 |
| Citation | Webster B, et al. (2018) Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses. Elife 7:e34273 |
| abstractText | Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections. |
