Inflammatory monocytes require type I interferon receptor signaling to activate NK cells via IL-18 during a mucosal viral infection

Amanda J. Lee, Branson Chen, Marianne V. Chew, Nicole G. Barra, Mira M. Shenouda, Tina Nham, Nico van Rooijen, Manel Jordana, Karen L. Mossman, Robert D. Schreiber, Matthias Mack, Ali A. Ashkar

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The requirement of type I interferon (IFN) for natural killer (NK) cell activation in response to viral infection is known, but the underlying mechanism remains unclear. Here, we demonstrate that type I IFN signaling in inflammatory monocytes, but not in dendritic cells (DCs) or NK cells, is essential for NK cell function in response to a mucosal herpes simplex virus type 2 (HSV-2) infection. Mice deficient in type I IFN signaling, Ifnar-/- and Irf9-/- mice, had significantly lower levels of inflammatory monocytes, were deficient in IL-18 production, and lacked NK cell-derived IFN-γ. Depletion of inflammatory monocytes, but not DCs or other myeloid cells, resulted in lower levels of IL-18 and a complete abrogation of NK cell function in HSV-2 infection. Moreover, this resulted in higher susceptibility to HSV-2 infection. Although Il18-/- mice had normal levels of inflammatory monocytes, their NK cells were unresponsive to HSV-2 challenge. This study highlights the importance of type I IFN signaling in inflammatory monocytes and the induction of the early innate antiviral response.

Original languageEnglish
Pages (from-to)1153-1167
Number of pages15
JournalJournal of Experimental Medicine
Volume214
Issue number4
DOIs
StatePublished - Apr 1 2017

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