Antigen specific immune response in Chlamydia muridarum genital infection is dependent on murine microRNAs-155 and -182.
Antigen specific immune response in Chlamydia muridarum genital infection is dependent on murine microRNAs-155 and -182.
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DOI：
10.18632/oncotarget.11461
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发表时间：
2016-10-04
期刊：
影响因子：
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通讯作者：
Arulanandam BP
中科院分区：
文献类型：
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作者：
Gupta R;Arkatkar T;Keck J;Koundinya GK;Castillo K;Hobel S;Chambers JP;Yu JJ;Guentzel MN;Aigner A;Christenson LK;Arulanandam BP
抗衣原体免疫涉及抗原（Ag）有效呈递至效应细胞，导致Ag特异性免疫应答。关于调节这些事件的内在基本机制的信息有限。本实验室先前的研究已经确定，选择microRNAs（miRs）的功能作为分子调节免疫的衣原体（Cm）生殖器感染。在这份报告中，我们研究了免疫细胞类型特异性miR，即miR-155和-182，以及在Ag特异性免疫中的作用。我们观察到miR-155在C57 BL/6骨髓来源的树突状细胞（BMDC）中显著上调，miR-182在脾Ag特异性CD 4 + T细胞中显著上调。使用模拟物和抑制剂，我们确定miR-155有助于Cm感染后BMDC活化。在BMDC中过表达的miR-155和在Ag特异性CD 4 + T细胞中过表达的miR-182的共培养物，或miR-155−/− BMDC与miR-182抑制剂处理的Ag特异性CD 4 + T细胞的共培养物，导致IFN-γ的产生与从Cm感染小鼠中分离的Ag特异性CD 4 + T细胞相当。此外，miR-182在鼻内接种疫苗的小鼠中显著上调，以保护免受Cm感染。在Cm感染的小鼠中，miR-182的体内消耗导致Ag特异性IFN-γ和生殖器病理学的减少。据我们所知，这是第一项报道miR-155（在感染Cm的DC中）和miR-182（在CD 4 + T细胞中）相互作用导致针对生殖器Cm的Ag特异性免疫应答的研究。
Anti-chlamydial immunity involves efficient presentation of antigens (Ag) to effector cells resulting in Ag-specific immune responses. There is limited information on inherent underlying mechanisms regulating these events. Previous studies from our laboratory have established that select microRNAs (miRs) function as molecular regulators of immunity in Chlamydia muridarum (Cm) genital infection. In this report, we investigated immune cell type-specific miRs, i.e. miR-155 and -182, and the role in Ag-specific immunity. We observed significant up-regulation of miR-155 in C57BL/6 bone marrow derived dendritic cells (BMDC), and miR-182 in splenic Ag-specific CD4+ T-cells. Using mimics and inhibitors, we determined that miR-155 contributed to BMDC activation following Cm infection. Co-cultures of miR-155 over-expressed in BMDC and miR-182 over-expressed in Ag-specific CD4+ T-cells, or miR-155−/− BMDC with miR-182 inhibitor treated Ag-specific CD4+ T-cells, resulted in IFN-γ production comparable to Ag-specific CD4+ T-cells isolated from Cm infected mice. Additionally, miR-182 was significantly up-regulated in intranasally vaccinated mice protected against Cm infection. In vivo depletion of miR-182 resulted in reduction in Ag-specific IFN-γ and genital pathology in Cm infected mice. To the best of our knowledge, this is the first study to report an interaction of miR-155 (in Cm infected DC) and miR-182 (in CD4+ T-cell) resulting in Ag specific immune responses against genital Cm.