Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation
The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective anti-viral responses in vivo is not fully understood. Cytokine response modifier D (CrmD) is a secreted receptor for TNF and lymphotoxin containing the smallpox virus-encoded chemokine receptor (SECRET) domain and is expressed by ectromelia virus, the causative agent of the smallpox-like disease mousepox. Here we show that CrmD is an essential virulence factor that controls natural killer cell activation and allows progression of fatal mousepox, and demonstrate that both SECRET and TNF binding domains are required for full CrmD activity. Vaccination with recombinant CrmD protects animals from lethal mousepox. These results indicate that a specific set of chemokines enhance the inflammatory and protective anti-viral responses mediated by TNF and lymphotoxin, and illustrate how viruses optimize anti-TNF strategies with the addition of a chemokine binding domain as soluble decoy receptors.
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Nature Research
2018
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Online Access: | http://hdl.handle.net/20.500.12792/500 http://hdl.handle.net/10261/291215 |
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dig-inia-es-10261-2912152023-02-20T07:15:48Z Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation Alejo Herberg, Ali Gabriel Ruiz-Argüello, M. B. Pontejo, S. M. Fernández De Marco, M. D. M. Saraiva, M. Hernáez, B. Alcamí, A. The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective anti-viral responses in vivo is not fully understood. Cytokine response modifier D (CrmD) is a secreted receptor for TNF and lymphotoxin containing the smallpox virus-encoded chemokine receptor (SECRET) domain and is expressed by ectromelia virus, the causative agent of the smallpox-like disease mousepox. Here we show that CrmD is an essential virulence factor that controls natural killer cell activation and allows progression of fatal mousepox, and demonstrate that both SECRET and TNF binding domains are required for full CrmD activity. Vaccination with recombinant CrmD protects animals from lethal mousepox. These results indicate that a specific set of chemokines enhance the inflammatory and protective anti-viral responses mediated by TNF and lymphotoxin, and illustrate how viruses optimize anti-TNF strategies with the addition of a chemokine binding domain as soluble decoy receptors. 2023-02-20T07:15:48Z 2023-02-20T07:15:48Z 2018 artículo Nature Communications 9: e1790 (2018) http://hdl.handle.net/20.500.12792/500 http://hdl.handle.net/10261/291215 10.1038/s41467-018-04098-8 2041-1723 en open Nature Research |
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The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective anti-viral responses in vivo is not fully understood. Cytokine response modifier D (CrmD) is a secreted receptor for TNF and lymphotoxin containing the smallpox virus-encoded chemokine receptor (SECRET) domain and is expressed by ectromelia virus, the causative agent of the smallpox-like disease mousepox. Here we show that CrmD is an essential virulence factor that controls natural killer cell activation and allows progression of fatal mousepox, and demonstrate that both SECRET and TNF binding domains are required for full CrmD activity. Vaccination with recombinant CrmD protects animals from lethal mousepox. These results indicate that a specific set of chemokines enhance the inflammatory and protective anti-viral responses mediated by TNF and lymphotoxin, and illustrate how viruses optimize anti-TNF strategies with the addition of a chemokine binding domain as soluble decoy receptors. |
format |
artículo |
author |
Alejo Herberg, Ali Gabriel Ruiz-Argüello, M. B. Pontejo, S. M. Fernández De Marco, M. D. M. Saraiva, M. Hernáez, B. Alcamí, A. |
spellingShingle |
Alejo Herberg, Ali Gabriel Ruiz-Argüello, M. B. Pontejo, S. M. Fernández De Marco, M. D. M. Saraiva, M. Hernáez, B. Alcamí, A. Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation |
author_facet |
Alejo Herberg, Ali Gabriel Ruiz-Argüello, M. B. Pontejo, S. M. Fernández De Marco, M. D. M. Saraiva, M. Hernáez, B. Alcamí, A. |
author_sort |
Alejo Herberg, Ali Gabriel |
title |
Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation |
title_short |
Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation |
title_full |
Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation |
title_fullStr |
Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation |
title_full_unstemmed |
Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation |
title_sort |
chemokines cooperate with tnf to provide protective anti-viral immunity and to enhance inflammation |
publisher |
Nature Research |
publishDate |
2018 |
url |
http://hdl.handle.net/20.500.12792/500 http://hdl.handle.net/10261/291215 |
work_keys_str_mv |
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1767603187151273984 |