Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ Production
NK cells are a key antiviral component of the innate immune response to HSV-2, particularly through their production of IFN-γ. It is still commonly thought that type I IFN activates NK cell function; however, rather than requiring the type I IFN receptor themselves, we have previously found that typ...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-06-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01261/full |
| _version_ | 1818541869343178752 |
|---|---|
| author | Amanda J. Lee Firoz Mian Sophie M. Poznanski Michele Stackaruk Tiffany Chan Marianne V. Chew Ali A. Ashkar |
| author_facet | Amanda J. Lee Firoz Mian Sophie M. Poznanski Michele Stackaruk Tiffany Chan Marianne V. Chew Ali A. Ashkar |
| author_sort | Amanda J. Lee |
| collection | DOAJ |
| description | NK cells are a key antiviral component of the innate immune response to HSV-2, particularly through their production of IFN-γ. It is still commonly thought that type I IFN activates NK cell function; however, rather than requiring the type I IFN receptor themselves, we have previously found that type I IFN activates NK cells through an indirect mechanism involving inflammatory monocytes and IL-18. Here, we further show that direct action of type I IFN on NK cells, rather than inducing IFN-γ, negatively regulates its production during HSV-2 infection and cytokine stimulation. During infection, IFN-γ is rapidly induced from NK cells at day 2 post-infection and then immediately downregulated at day 3 post-infection. We found that this downregulation of IFN-γ release was not due to a loss of NK cells at day 3 post-infection, but negatively regulated through IFN signaling on NK cells. Absence of IFNAR on NK cells led to a significantly increased level of IFN-γ compared to WT NK cells after HSV-2 infection in vitro. Further, priming of NK cells with type I IFN was able to suppress cytokine-induced IFN-γ production from both human and mouse NK cells. We found that this immunosuppression was not mediated by IL-10. Rather, we found that type I IFN induced a significant increase in Axl expression on human NK cells. Overall, our data suggests that type I IFN negatively regulates NK cell IFN-γ production through a direct mechanism in vitro and during HSV-2 infection. |
| first_indexed | 2024-12-11T22:14:47Z |
| format | Article |
| id | doaj.art-afa462e16097466aaae09852f512e2ee |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T22:14:47Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-afa462e16097466aaae09852f512e2ee2022-12-22T00:48:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01261441419Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ ProductionAmanda J. LeeFiroz MianSophie M. PoznanskiMichele StackarukTiffany ChanMarianne V. ChewAli A. AshkarNK cells are a key antiviral component of the innate immune response to HSV-2, particularly through their production of IFN-γ. It is still commonly thought that type I IFN activates NK cell function; however, rather than requiring the type I IFN receptor themselves, we have previously found that type I IFN activates NK cells through an indirect mechanism involving inflammatory monocytes and IL-18. Here, we further show that direct action of type I IFN on NK cells, rather than inducing IFN-γ, negatively regulates its production during HSV-2 infection and cytokine stimulation. During infection, IFN-γ is rapidly induced from NK cells at day 2 post-infection and then immediately downregulated at day 3 post-infection. We found that this downregulation of IFN-γ release was not due to a loss of NK cells at day 3 post-infection, but negatively regulated through IFN signaling on NK cells. Absence of IFNAR on NK cells led to a significantly increased level of IFN-γ compared to WT NK cells after HSV-2 infection in vitro. Further, priming of NK cells with type I IFN was able to suppress cytokine-induced IFN-γ production from both human and mouse NK cells. We found that this immunosuppression was not mediated by IL-10. Rather, we found that type I IFN induced a significant increase in Axl expression on human NK cells. Overall, our data suggests that type I IFN negatively regulates NK cell IFN-γ production through a direct mechanism in vitro and during HSV-2 infection.https://www.frontiersin.org/article/10.3389/fimmu.2019.01261/fullNK cellstype I IFNIFN-γHSVHuman NK cells |
| spellingShingle | Amanda J. Lee Firoz Mian Sophie M. Poznanski Michele Stackaruk Tiffany Chan Marianne V. Chew Ali A. Ashkar Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ Production Frontiers in Immunology NK cells type I IFN IFN-γ HSV Human NK cells |
| title | Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ Production |
| title_full | Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ Production |
| title_fullStr | Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ Production |
| title_full_unstemmed | Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ Production |
| title_short | Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ Production |
| title_sort | type i interferon receptor on nk cells negatively regulates interferon γ production |
| topic | NK cells type I IFN IFN-γ HSV Human NK cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01261/full |
| work_keys_str_mv | AT amandajlee typeiinterferonreceptoronnkcellsnegativelyregulatesinterferongproduction AT firozmian typeiinterferonreceptoronnkcellsnegativelyregulatesinterferongproduction AT sophiempoznanski typeiinterferonreceptoronnkcellsnegativelyregulatesinterferongproduction AT michelestackaruk typeiinterferonreceptoronnkcellsnegativelyregulatesinterferongproduction AT tiffanychan typeiinterferonreceptoronnkcellsnegativelyregulatesinterferongproduction AT mariannevchew typeiinterferonreceptoronnkcellsnegativelyregulatesinterferongproduction AT aliaashkar typeiinterferonreceptoronnkcellsnegativelyregulatesinterferongproduction |