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Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses

2018; eLife Sciences Publications Ltd; Volume: 7; Linguagem: Inglês

10.7554/elife.34273

2050-084X

Brian Webster, Scott Werneke, Biljana Zafirova, Sébastien This, Séverin Coléon, Élodie Décembre, Helena Païdassi, Isabelle Bouvier, Pierre-Emmanuel Joubert, Darragh Duffy, Thierry Walzer, Matthew L. Albert, Marlène Dreux,

interferon and immune responses

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.