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

Abstract : 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.
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Submitted on : Monday, June 25, 2018 - 2:58:19 PM
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Brian Webster, Scott Werneke, Biljana Zafirova, Sebastien This, Séverin Coléon, et al.. Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses. eLife, eLife Sciences Publication, 2018, 7, pp.e34273. ⟨10.7554/eLife.34273⟩. ⟨pasteur-01822838⟩

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