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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...

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Autores principales: Szulc-Dąbrowska, Lidia, Struzik, Justyna, Ostrowska, Agnieszka, Guzera, Maciej, Toka, Felix N., Bossowska-Nowicka, Magdalena, Gieryńska, Małgorzata M., Winnicka, Anna, Nowak, Zuzanna, Niemiałtowski, Marek G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467855/
https://www.ncbi.nlm.nih.gov/pubmed/28604814
http://dx.doi.org/10.1371/journal.pone.0179166
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author Szulc-Dąbrowska, Lidia
Struzik, Justyna
Ostrowska, Agnieszka
Guzera, Maciej
Toka, Felix N.
Bossowska-Nowicka, Magdalena
Gieryńska, Małgorzata M.
Winnicka, Anna
Nowak, Zuzanna
Niemiałtowski, Marek G.
author_facet Szulc-Dąbrowska, Lidia
Struzik, Justyna
Ostrowska, Agnieszka
Guzera, Maciej
Toka, Felix N.
Bossowska-Nowicka, Magdalena
Gieryńska, Małgorzata M.
Winnicka, Anna
Nowak, Zuzanna
Niemiałtowski, Marek G.
author_sort Szulc-Dąbrowska, Lidia
collection PubMed
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.
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spelling pubmed-54678552017-06-22 Functional paralysis of GM-CSF–derived bone marrow cells productively infected with ectromelia virus Szulc-Dąbrowska, Lidia Struzik, Justyna Ostrowska, Agnieszka Guzera, Maciej Toka, Felix N. Bossowska-Nowicka, Magdalena Gieryńska, Małgorzata M. Winnicka, Anna Nowak, Zuzanna Niemiałtowski, Marek G. PLoS One Research Article 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. Public Library of Science 2017-06-12 /pmc/articles/PMC5467855/ /pubmed/28604814 http://dx.doi.org/10.1371/journal.pone.0179166 Text en © 2017 Szulc-Dąbrowska et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Szulc-Dąbrowska, Lidia
Struzik, Justyna
Ostrowska, Agnieszka
Guzera, Maciej
Toka, Felix N.
Bossowska-Nowicka, Magdalena
Gieryńska, Małgorzata M.
Winnicka, Anna
Nowak, Zuzanna
Niemiałtowski, Marek G.
Functional paralysis of GM-CSF–derived bone marrow cells productively infected with ectromelia virus
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467855/
https://www.ncbi.nlm.nih.gov/pubmed/28604814
http://dx.doi.org/10.1371/journal.pone.0179166
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