Lee, Amanda J. and Chen, Branson and Chew, Marianne V. and Barra, Nicole G. and Shenouda, Mira M. and Nham, Tina and van Rooijen, Nico and Jordana, Manel and Mossman, Karen L. and Schreiber, Robert D. and Mack, Matthias and Ashkar, Ali A. (2017) Inflammatory monocytes require type I interferon receptor signaling to activate NK cells via IL-18 during a mucosal viral infection. JOURNAL OF EXPERIMENTAL MEDICINE, 214 (4). pp. 1153-1167. ISSN 0022-1007, 1540-9538
Full text not available from this repository. (Request a copy)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-gamma. 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NATURAL-KILLER-CELLS; SIMPLEX-VIRUS TYPE-2; TOLL-LIKE RECEPTOR; DENDRITIC CELLS; INNATE PROTECTION; GAMMA; MICE; RESPONSES; IMMUNITY; INTERLEUKIN-15; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:00 |
| Last Modified: | 27 Feb 2019 14:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/178 |
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