Activation mechanisms of natural killer cells during influenza virus infection.
During early viral infection, activation of natural killer (NK) cells elicits the effector functions of target cell lysis and cytokine production. However, the cellular and molecular mechanisms leading to NK cell activation during viral infections are incompletely understood. In this study, using a...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3534084?pdf=render |
| _version_ | 1818999161829195776 |
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| author | Ilwoong Hwang Jeannine M Scott Tejaswi Kakarla David M Duriancik Seohyun Choi Chunghwan Cho Taehyung Lee Hyojin Park Anthony R French Eleni Beli Elizabeth Gardner Sungjin Kim |
| author_facet | Ilwoong Hwang Jeannine M Scott Tejaswi Kakarla David M Duriancik Seohyun Choi Chunghwan Cho Taehyung Lee Hyojin Park Anthony R French Eleni Beli Elizabeth Gardner Sungjin Kim |
| author_sort | Ilwoong Hwang |
| collection | DOAJ |
| description | During early viral infection, activation of natural killer (NK) cells elicits the effector functions of target cell lysis and cytokine production. However, the cellular and molecular mechanisms leading to NK cell activation during viral infections are incompletely understood. In this study, using a model of acute viral infection, we investigated the mechanisms controlling cytotoxic activity and cytokine production in response to influenza (flu) virus. Analysis of cytokine receptor deficient mice demonstrated that type I interferons (IFNs), but not IL-12 or IL-18, were critical for the NK cell expression of both IFN-γ and granzyme B in response to flu infection. Further, adoptive transfer experiments revealed that NK cell activation was mediated by type I IFNs acting directly on NK cells. Analysis of signal transduction molecules showed that during flu infection, STAT1 activation in NK cells was completely dependent on direct type I IFN signaling, whereas STAT4 activation was only partially dependent. In addition, granzyme B induction in NK cells was mediated by signaling primarily through STAT1, but not STAT4, while IFN-γ production was mediated by signaling through STAT4, but not STAT1. Therefore, our findings demonstrate the importance of direct action of type I IFNs on NK cells to mount effective NK cell responses in the context of flu infection and delineate NK cell signaling pathways responsible for controlling cytotoxic activity and cytokine production. |
| first_indexed | 2024-12-20T22:13:02Z |
| format | Article |
| id | doaj.art-276c28f4e1f34223991f6a1060dff4f3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T22:13:02Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-276c28f4e1f34223991f6a1060dff4f32022-12-21T19:25:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5185810.1371/journal.pone.0051858Activation mechanisms of natural killer cells during influenza virus infection.Ilwoong HwangJeannine M ScottTejaswi KakarlaDavid M DuriancikSeohyun ChoiChunghwan ChoTaehyung LeeHyojin ParkAnthony R FrenchEleni BeliElizabeth GardnerSungjin KimDuring early viral infection, activation of natural killer (NK) cells elicits the effector functions of target cell lysis and cytokine production. However, the cellular and molecular mechanisms leading to NK cell activation during viral infections are incompletely understood. In this study, using a model of acute viral infection, we investigated the mechanisms controlling cytotoxic activity and cytokine production in response to influenza (flu) virus. Analysis of cytokine receptor deficient mice demonstrated that type I interferons (IFNs), but not IL-12 or IL-18, were critical for the NK cell expression of both IFN-γ and granzyme B in response to flu infection. Further, adoptive transfer experiments revealed that NK cell activation was mediated by type I IFNs acting directly on NK cells. Analysis of signal transduction molecules showed that during flu infection, STAT1 activation in NK cells was completely dependent on direct type I IFN signaling, whereas STAT4 activation was only partially dependent. In addition, granzyme B induction in NK cells was mediated by signaling primarily through STAT1, but not STAT4, while IFN-γ production was mediated by signaling through STAT4, but not STAT1. Therefore, our findings demonstrate the importance of direct action of type I IFNs on NK cells to mount effective NK cell responses in the context of flu infection and delineate NK cell signaling pathways responsible for controlling cytotoxic activity and cytokine production.http://europepmc.org/articles/PMC3534084?pdf=render |
| spellingShingle | Ilwoong Hwang Jeannine M Scott Tejaswi Kakarla David M Duriancik Seohyun Choi Chunghwan Cho Taehyung Lee Hyojin Park Anthony R French Eleni Beli Elizabeth Gardner Sungjin Kim Activation mechanisms of natural killer cells during influenza virus infection. PLoS ONE |
| title | Activation mechanisms of natural killer cells during influenza virus infection. |
| title_full | Activation mechanisms of natural killer cells during influenza virus infection. |
| title_fullStr | Activation mechanisms of natural killer cells during influenza virus infection. |
| title_full_unstemmed | Activation mechanisms of natural killer cells during influenza virus infection. |
| title_short | Activation mechanisms of natural killer cells during influenza virus infection. |
| title_sort | activation mechanisms of natural killer cells during influenza virus infection |
| url | http://europepmc.org/articles/PMC3534084?pdf=render |
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