Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2
Marek’s disease virus (MDV), an avian alphaherpesvirus, infects chickens, transforms CD4+ T cells, and induces immunosuppression early during infection. However, the exact mechanisms involved in MDV-induced immunosuppression are yet to be identified. Here, our results demonstrate that MDV infection...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.801781/full |
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| author | Nitin Kamble Angila Gurung Angila Gurung Benedikt B. Kaufer Ansar Ahmed Pathan Shahriar Behboudi Shahriar Behboudi |
| author_facet | Nitin Kamble Angila Gurung Angila Gurung Benedikt B. Kaufer Ansar Ahmed Pathan Shahriar Behboudi Shahriar Behboudi |
| author_sort | Nitin Kamble |
| collection | DOAJ |
| description | Marek’s disease virus (MDV), an avian alphaherpesvirus, infects chickens, transforms CD4+ T cells, and induces immunosuppression early during infection. However, the exact mechanisms involved in MDV-induced immunosuppression are yet to be identified. Here, our results demonstrate that MDV infection in vitro and in vivo induces activation of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). This exerts its inhibitory effects on T cell proliferation at day 21 post infection via PGE2 receptor 2 (EP2) and receptor 4 (EP4). Impairment of the MDV-induced T cell proliferation was associated with downregulation of IL-2 and transferrin uptake in a COX-2/PGE2 dependent manner in vitro. Interestingly, oral administration of a COX-2 inhibitor, meloxicam, during MDV infection inhibited COX-2 activation and rescued T cell proliferation at day 21 post infection. Taken together, our results reveal a novel mechanism that contributes to immunosuppression in the MDV-infected chickens. |
| first_indexed | 2024-12-24T11:15:48Z |
| format | Article |
| id | doaj.art-8ef9b155eae1450fb46c81651de219ee |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T11:15:48Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8ef9b155eae1450fb46c81651de219ee2022-12-21T16:58:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.801781801781Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2Nitin Kamble0Angila Gurung1Angila Gurung2Benedikt B. Kaufer3Ansar Ahmed Pathan4Shahriar Behboudi5Shahriar Behboudi6The Pirbright Institute, Woking, United KingdomThe Pirbright Institute, Woking, United KingdomDepartment of Life Sciences, College of Health and Life Sciences, Brunel University, London, United KingdomInstitut für Virologie, Freie Universität Berlin, Berlin, GermanyDepartment of Life Sciences, College of Health and Life Sciences, Brunel University, London, United KingdomThe Pirbright Institute, Woking, United KingdomFaculty of Health and Medical Sciences, School of Veterinary Medicine, University of Surrey, Guildford, United KingdomMarek’s disease virus (MDV), an avian alphaherpesvirus, infects chickens, transforms CD4+ T cells, and induces immunosuppression early during infection. However, the exact mechanisms involved in MDV-induced immunosuppression are yet to be identified. Here, our results demonstrate that MDV infection in vitro and in vivo induces activation of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). This exerts its inhibitory effects on T cell proliferation at day 21 post infection via PGE2 receptor 2 (EP2) and receptor 4 (EP4). Impairment of the MDV-induced T cell proliferation was associated with downregulation of IL-2 and transferrin uptake in a COX-2/PGE2 dependent manner in vitro. Interestingly, oral administration of a COX-2 inhibitor, meloxicam, during MDV infection inhibited COX-2 activation and rescued T cell proliferation at day 21 post infection. Taken together, our results reveal a novel mechanism that contributes to immunosuppression in the MDV-infected chickens.https://www.frontiersin.org/articles/10.3389/fimmu.2021.801781/fullMarek’s disease virusT cell proliferationCOX2 = cyclooxygenase 2PGE2immunosuppression |
| spellingShingle | Nitin Kamble Angila Gurung Angila Gurung Benedikt B. Kaufer Ansar Ahmed Pathan Shahriar Behboudi Shahriar Behboudi Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2 Frontiers in Immunology Marek’s disease virus T cell proliferation COX2 = cyclooxygenase 2 PGE2 immunosuppression |
| title | Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2 |
| title_full | Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2 |
| title_fullStr | Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2 |
| title_full_unstemmed | Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2 |
| title_short | Marek’s Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2 |
| title_sort | marek s disease virus modulates t cell proliferation via activation of cyclooxygenase 2 dependent prostaglandin e2 |
| topic | Marek’s disease virus T cell proliferation COX2 = cyclooxygenase 2 PGE2 immunosuppression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.801781/full |
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