Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence.
CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (I...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-12-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006050&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849472683924783104 |
|---|---|
| author | Mathew Clement Morgan Marsden Maria A Stacey Juneid Abdul-Karim Silvia Gimeno Brias Diana Costa Bento Martin J Scurr Peter Ghazal Casey T Weaver Gianluca Carlesso Simon Clare Simon A Jones Andrew Godkin Gareth W Jones Ian R Humphreys |
| author_facet | Mathew Clement Morgan Marsden Maria A Stacey Juneid Abdul-Karim Silvia Gimeno Brias Diana Costa Bento Martin J Scurr Peter Ghazal Casey T Weaver Gianluca Carlesso Simon Clare Simon A Jones Andrew Godkin Gareth W Jones Ian R Humphreys |
| author_sort | Mathew Clement |
| collection | DOAJ |
| description | CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva. Thus, IL-10+CD4+ T cells suppress antiviral immune responses against CMV. Expansion of this T-cell population in the periphery was promoted by IL-27 whereas mucosal IL-10+ T cell responses were ICOS-dependent. Infected Il27rα-deficient mice with reduced peripheral IL-10+CD4+ T cell accumulation displayed robust T cell responses and restricted MCMV persistence and shedding. Temporal inhibition experiments revealed that IL-27R signaling during initial infection was required for the suppression of T cell immunity and control of virus shedding during MCMV persistence. IL-27 production was promoted by type-I IFN, suggesting that β-herpesviridae exploit the immune-regulatory properties of this antiviral pathway to establish chronicity. Further, our data reveal that cytokine signaling events during initial infection profoundly influence virus chronicity. |
| format | Article |
| id | doaj-art-7fe395ac2dd442b6bb7558097586ab3e |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2016-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-7fe395ac2dd442b6bb7558097586ab3e2025-08-20T03:24:27ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-12-011212e100605010.1371/journal.ppat.1006050Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence.Mathew ClementMorgan MarsdenMaria A StaceyJuneid Abdul-KarimSilvia Gimeno BriasDiana Costa BentoMartin J ScurrPeter GhazalCasey T WeaverGianluca CarlessoSimon ClareSimon A JonesAndrew GodkinGareth W JonesIan R HumphreysCD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva. Thus, IL-10+CD4+ T cells suppress antiviral immune responses against CMV. Expansion of this T-cell population in the periphery was promoted by IL-27 whereas mucosal IL-10+ T cell responses were ICOS-dependent. Infected Il27rα-deficient mice with reduced peripheral IL-10+CD4+ T cell accumulation displayed robust T cell responses and restricted MCMV persistence and shedding. Temporal inhibition experiments revealed that IL-27R signaling during initial infection was required for the suppression of T cell immunity and control of virus shedding during MCMV persistence. IL-27 production was promoted by type-I IFN, suggesting that β-herpesviridae exploit the immune-regulatory properties of this antiviral pathway to establish chronicity. Further, our data reveal that cytokine signaling events during initial infection profoundly influence virus chronicity.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006050&type=printable |
| spellingShingle | Mathew Clement Morgan Marsden Maria A Stacey Juneid Abdul-Karim Silvia Gimeno Brias Diana Costa Bento Martin J Scurr Peter Ghazal Casey T Weaver Gianluca Carlesso Simon Clare Simon A Jones Andrew Godkin Gareth W Jones Ian R Humphreys Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence. PLoS Pathogens |
| title | Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence. |
| title_full | Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence. |
| title_fullStr | Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence. |
| title_full_unstemmed | Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence. |
| title_short | Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence. |
| title_sort | cytomegalovirus specific il 10 producing cd4 t cells are governed by type i ifn induced il 27 and promote virus persistence |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006050&type=printable |
| work_keys_str_mv | AT mathewclement cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT morganmarsden cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT mariaastacey cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT juneidabdulkarim cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT silviagimenobrias cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT dianacostabento cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT martinjscurr cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT peterghazal cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT caseytweaver cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT gianlucacarlesso cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT simonclare cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT simonajones cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT andrewgodkin cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT garethwjones cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence AT ianrhumphreys cytomegalovirusspecificil10producingcd4tcellsaregovernedbytypeiifninducedil27andpromoteviruspersistence |