Title | Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Seelige R, Saddawi-Konefka R, Adams NM, Picarda G, Sun JC, Benedict CA, Bui JD |
Journal | Sci Rep |
Volume | 8 |
Issue | 1 |
Pagination | 13670 |
Date Published | 2018 09 12 |
ISSN | 2045-2322 |
Keywords | Animals, Cell Line, Tumor, Enzyme Inhibitors, Herpesviridae Infections, Hydroquinones, Immunity, Innate, Interleukin-17, Killer Cells, Natural, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Muromegalovirus, Neutrophils, NF-E2-Related Factor 2, RNA Interference, RNA, Small Interfering |
Abstract | Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses. |
DOI | 10.1038/s41598-018-32011-2 |
Alternate Journal | Sci Rep |
PubMed ID | 30209334 |
PubMed Central ID | PMC6135835 |
Grant List | R01 AI101423 / AI / NIAID NIH HHS / United States R01 AI100874 / AI / NIAID NIH HHS / United States R21 AI113349 / AI / NIAID NIH HHS / United States R01 CA157885 / CA / NCI NIH HHS / United States U42 OD012210 / OD / NIH HHS / United States R56 AI101423 / AI / NIAID NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
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