Prostaglandin E2-Induced Immune Suppression via Cytotoxic T-Lymphocyte Antigen 4 in Paratuberculosis
Prostaglandin E2-Induced Immune Suppression via Cytotoxic T-Lymphocyte Antigen 4 in Paratuberculosis
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DOI：
10.1128/iai.00210-22
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发表时间：
2022-09-14
影响因子：
3.1
通讯作者：
Ohashi，Kazuhiko
中科院分区：
文献类型：
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作者：
Sajiki，Yamato;Konnai，Satoru;Ohashi，Kazuhiko
副结核病是由兼性细胞内病原体鸟分枝杆菌副结核亚种引起的反刍动物慢性肠炎。Th 1应答抑制M.在亚临床早期阶段，然而，我们先前已经表明免疫抑制分子，如前列腺素E2（PGE 2），抑制M。禽副结核亚种特异性Th 1应答。迄今为止，M.禽副结核亚种感染尚未阐明。因此，在本研究中，我们研究了副结核病牛外周血单个核细胞（PBMC）表达的细胞毒性T淋巴细胞抗原4（CTLA-4）的功能，因为已知在M.副结核亚种实验感染M.副结核分枝杆菌抗原诱导实验感染牛T细胞表达CTLA-4。副结核亚种有趣的是，PGE 2和E前列腺素4激动剂也诱导T细胞中CTLA-4的表达。此外，用牛CTLA-4-免疫球蛋白融合蛋白（CTLA-4-IG）进行的功能测定表明，CTLA-4抑制M中γ干扰素（IFN-γ）的产生。抗牛CTLA-4单克隆抗体阻断后，IFN-γ和肿瘤坏死因子α的分泌增加。这些初步结果表明PGE 2通过CTLA-4对M.副结核亚种因此，有必要在未来澄清CTLA-4介导的免疫抑制是否促进牛副结核病的疾病进展。
Paratuberculosis is a chronic enteritis of ruminants caused by the facultative intracellular pathogen Mycobacterium avium subsp.paratuberculosis. The Th1 response inhibits the proliferation of M. avium subsp.paratuberculosisduring the early subclinical stage. However, we have previously shown that immune inhibitory molecules, such as prostaglandin E2(PGE2), suppress M. avium subsp.paratuberculosis-specific Th1 responses as the disease progresses. To date, the mechanism underlying immunosuppression during M. avium subsp.paratuberculosisinfection has not been elucidated. Therefore, in the present study, we investigated the function of cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed by peripheral blood mononuclear cells (PBMCs) from cattle with paratuberculosis because CTLA-4 expression is known to be elevated in T cells under an M. avium subsp.paratuberculosisexperimental infection. M. avium subsp.paratuberculosisantigen induced CTLA-4 expression in T cells from cattle experimentally infected with M. avium subsp.paratuberculosis. Interestingly, both PGE2and an E prostanoid 4 agonist also induced CTLA-4 expression in T cells. In addition, a functional assay with a bovine CTLA-4-immunogobulin fusion protein (CTLA-4-Ig) indicated that CTLA-4 inhibited gamma interferon (IFN-γ) production in M. avium subsp.paratuberculosis-stimulated PBMCs, while blockade by anti-bovine CTLA-4 monoclonal antibody increased the secretion of IFN-γ and tumor necrosis factor alpha production in these PBMCs. These preliminary findings show that PGE2has immunosuppressive effects via CTLA-4 to M. avium subsp.paratuberculosis. Therefore, it is necessary to clarify in the future whether CTLA-4-mediated immunosuppression facilitates disease progression of paratuberculosis in cattle.