Marek's Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2.

Marek's Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2.
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DOI:
10.3389/fimmu.2021.801781
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发表时间:
2021
影响因子:
7.3
通讯作者:
Behboudi S
Behboudi S
中科院分区:
医学2区
文献类型:
--
作者:
Kamble N;Gurung A;Kaufer BB;Pathan AA;Behboudi S

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马立克氏病病毒(MDV)是一种禽类α疱疹病毒,感染鸡,转化CD 4 + T细胞,并在感染早期诱导免疫抑制。然而,MDV诱导的免疫抑制的确切机制尚未确定。在此,我们的研究结果表明,MDV感染在体外和体内诱导环氧合酶-2(考克斯-2)的激活和前列腺素E2(PGE 2)的产生。这通过PGE 2受体2(EP 2)和受体4(EP 4)在感染后第21天对T细胞增殖发挥其抑制作用。MDV诱导的T细胞增殖的损害与IL-2和转铁蛋白摄取的下调有关,在体外以考克斯-2/PGE 2依赖的方式。有趣的是,MDV感染期间口服考克斯-2抑制剂美洛昔康可抑制考克斯-2活化,并在感染后第21天挽救T细胞增殖。综上所述,我们的研究结果揭示了一种新的机制,有助于在MDV感染的鸡免疫抑制。
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.
DOI: 10.3382/ps/pew158
发表时间: 2016-10-01
期刊: POULTRY SCIENCE
影响因子: 4.4
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