Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus.
Ectromelia virus (ECTV) is an orthopoxvirus responsible for mousepox, a lethal disease of certain strains of mice that is similar to smallpox in humans, caused by variola virus (VARV). ECTV, similar to VARV, exhibits a narrow host range and has co-evolved with its natural host. Consequently, ECTV em...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5467855?pdf=render |
| _version_ | 1819039337146220544 |
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| author | Lidia Szulc-Dąbrowska Justyna Struzik Agnieszka Ostrowska Maciej Guzera Felix N Toka Magdalena Bossowska-Nowicka Małgorzata M Gieryńska Anna Winnicka Zuzanna Nowak Marek G Niemiałtowski |
| author_facet | Lidia Szulc-Dąbrowska Justyna Struzik Agnieszka Ostrowska Maciej Guzera Felix N Toka Magdalena Bossowska-Nowicka Małgorzata M Gieryńska Anna Winnicka Zuzanna Nowak Marek G Niemiałtowski |
| author_sort | Lidia Szulc-Dąbrowska |
| collection | DOAJ |
| description | Ectromelia virus (ECTV) is an orthopoxvirus responsible for mousepox, a lethal disease of certain strains of mice that is similar to smallpox in humans, caused by variola virus (VARV). ECTV, similar to VARV, exhibits a narrow host range and has co-evolved with its natural host. Consequently, ECTV employs sophisticated and host-specific strategies to control the immune cells that are important for induction of antiviral immune response. In the present study we investigated the influence of ECTV infection on immune functions of murine GM-CSF-derived bone marrow cells (GM-BM), comprised of conventional dendritic cells (cDCs) and macrophages. Our results showed for the first time that ECTV is able to replicate productively in GM-BM and severely impaired their innate and adaptive immune functions. Infected GM-BM exhibited dramatic changes in morphology and increased apoptosis during the late stages of infection. Moreover, GM-BM cells were unable to uptake and process antigen, reach full maturity and mount a proinflammatory response. Inhibition of cytokine/chemokine response may result from the alteration of nuclear translocation of NF-κB, IRF3 and IRF7 transcription factors and down-regulation of many genes involved in TLR, RLR, NLR and type I IFN signaling pathways. Consequently, GM-BM show inability to stimulate proliferation of purified allogeneic CD4+ T cells in a primary mixed leukocyte reaction (MLR). Taken together, our data clearly indicate that ECTV induces immunosuppressive mechanisms in GM-BM leading to their functional paralysis, thus compromising their ability to initiate downstream T-cell activation events. |
| first_indexed | 2024-12-21T08:51:36Z |
| format | Article |
| id | doaj.art-0f192d49face46bcb48c08b4f0cafe9a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T08:51:36Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0f192d49face46bcb48c08b4f0cafe9a2022-12-21T19:09:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017916610.1371/journal.pone.0179166Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus.Lidia Szulc-DąbrowskaJustyna StruzikAgnieszka OstrowskaMaciej GuzeraFelix N TokaMagdalena Bossowska-NowickaMałgorzata M GieryńskaAnna WinnickaZuzanna NowakMarek G NiemiałtowskiEctromelia virus (ECTV) is an orthopoxvirus responsible for mousepox, a lethal disease of certain strains of mice that is similar to smallpox in humans, caused by variola virus (VARV). ECTV, similar to VARV, exhibits a narrow host range and has co-evolved with its natural host. Consequently, ECTV employs sophisticated and host-specific strategies to control the immune cells that are important for induction of antiviral immune response. In the present study we investigated the influence of ECTV infection on immune functions of murine GM-CSF-derived bone marrow cells (GM-BM), comprised of conventional dendritic cells (cDCs) and macrophages. Our results showed for the first time that ECTV is able to replicate productively in GM-BM and severely impaired their innate and adaptive immune functions. Infected GM-BM exhibited dramatic changes in morphology and increased apoptosis during the late stages of infection. Moreover, GM-BM cells were unable to uptake and process antigen, reach full maturity and mount a proinflammatory response. Inhibition of cytokine/chemokine response may result from the alteration of nuclear translocation of NF-κB, IRF3 and IRF7 transcription factors and down-regulation of many genes involved in TLR, RLR, NLR and type I IFN signaling pathways. Consequently, GM-BM show inability to stimulate proliferation of purified allogeneic CD4+ T cells in a primary mixed leukocyte reaction (MLR). Taken together, our data clearly indicate that ECTV induces immunosuppressive mechanisms in GM-BM leading to their functional paralysis, thus compromising their ability to initiate downstream T-cell activation events.http://europepmc.org/articles/PMC5467855?pdf=render |
| spellingShingle | Lidia Szulc-Dąbrowska Justyna Struzik Agnieszka Ostrowska Maciej Guzera Felix N Toka Magdalena Bossowska-Nowicka Małgorzata M Gieryńska Anna Winnicka Zuzanna Nowak Marek G Niemiałtowski Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus. PLoS ONE |
| title | Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus. |
| title_full | Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus. |
| title_fullStr | Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus. |
| title_full_unstemmed | Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus. |
| title_short | Functional paralysis of GM-CSF-derived bone marrow cells productively infected with ectromelia virus. |
| title_sort | functional paralysis of gm csf derived bone marrow cells productively infected with ectromelia virus |
| url | http://europepmc.org/articles/PMC5467855?pdf=render |
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