Porcine Circovirus Type 2 Suppresses IL-12p40 Induction via Capsid/gC1qR-Mediated MicroRNAs and Signalings.
Porcine Circovirus Type 2 Suppresses IL-12p40 Induction via Capsid/gC1qR-Mediated MicroRNAs and Signalings.
复制标题
2 型猪圆环病毒通过衣壳/gC1qR 介导的 MicroRNA 和信号传导抑制 IL-12p40 诱导
DOI：
10.4049/jimmunol.1800250
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发表时间：
2018-07-15
期刊：
影响因子：
--
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Du Q;Wu X;Wang T;Yang X;Wang Z;Niu Y;Zhao X;Liu SL;Tong D;Huang Y
猪圆环病毒2型（Porcine Circovirus 2，PCV 2）是一种免疫抑制病原体，常被发现可增加其他病原体感染的风险。然而，决定PCV 2感染动物易感性的相关免疫机制仍不清楚。在这项研究中，我们证实，PCV 2感染抑制IL-12 p40的表达和宿主的Th 1免疫反应，导致削弱病原体清除后，猪繁殖呼吸综合征病毒（PRRSV）或副猪嗜血杆菌感染。PCV 2感染抑制病原体、LPS/IFN-γ或LPS/R848诱导的猪肺泡巨噬细胞中IL-12 p40的表达。PCV 2衣壳（Cap）是抑制LPS/IFN-γ、LPS/R848、PRRSV、H.副猪。无论是野生型PCV 2还是含有PCV 2 Cap的PCV 2-replicase 1和PCV 1-Cap 2突变体，都能显著降低IL-12 p40水平，并增加PRRSV和H.与模拟或PCV 1型感染相比，Cap结合蛋白gC 1 qR不参与IL-12 p40诱导，但介导PCV 2 Cap对IL-12 p40诱导的抑制作用。PCV 2还通过抑制NF-κB p65与IL-12 B启动子的结合以及上调miR-23 a和miR-29 B b来激活PI 3 K/Akt 1和p38 MAPK信号传导，从而抑制IL-12 p40的表达。敲低Akt 1和p38 MAPK可下调miR-23 a和miR-29 b，并增加IL-12 p40的表达。miR-23 a和miR-29 b的抑制减弱了PCV 2对IL-12 p40诱导的抑制作用，导致IL-12 p40表达和Th 1细胞群增加，并降低了对PRRSV或H.副猪。综上所述，这些结果表明，PCV 2感染通过gC 1 qR介导的PI 3 K/Akt 1和p38 MAPK信号转导激活抑制IL-12 p40表达，从而降低宿主Th 1免疫力，增加其他病原性感染的风险。
Porcine circovirus (PCV) type 2 (PCV2), an immunosuppression pathogen, is often found to increase the risk of other pathogenic infections. Yet the relative immune mechanisms determining the susceptibility of PCV2-infected animals remain unclear. In this study, we confirmed that PCV2 infection suppressed IL-12p40 expression and host Th1 immune response, leading to a weakened pathogenic clearance upon porcine reproductive respiratory syndrome virus (PRRSV) or Haemophilus parasuis infection. PCV2 infection suppressed pathogens, LPS/IFN-γ, or LPS/R848-induced IL-12p40 expression in porcine alveolar macrophages. PCV2 capsid (Cap) was the major component to suppress IL-12p40 induction by LPS/IFN-γ, LPS/R848, PRRSV, or H. parasuis. Either wild-type PCV2 or mutants PCV2–replicase 1 and PCV type 1–Cap2, which contained PCV2 Cap, significantly decreased IL-12p40 levels and increased the replication of PRRSV and H. parasuis in the lung tissues relative to mock or PCV type 1 infection. gC1qR, a Cap binding protein, was not involved in IL-12p40 induction but mediated the inhibitory effect of PCV2 Cap on IL-12p40 induction. PCV2 also activated PI3K/Akt1 and p38 MAPK signalings to inhibit IL-12p40 expression via inhibition of NF-κB p65 binding to il12B promoter and upregulation of miR-23a and miR-29b. Knockdown of Akt1 and p38 MAPK downregulated miR-23a and miR-29b and increased IL-12p40 expression. Inhibition of miR-23a and miR-29b attenuated the inhibitory effect of PCV2 on IL-12p40 induction, resulting in an increased IL-12p40 expression and Th1 cell population and reduced susceptibility to PRRSV or H. parasuis. Taken together, these results demonstrate that PCV2 infection suppresses IL-12p40 expression to lower host Th1 immunity to increase the risk of other pathogenic infection via gC1qR-mediated PI3K/Akt1 and p38 MAPK signaling activation.
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影响因子：
3.6
作者：
Pednekar L;Valentino A;Ji Y;Tumma N;Valentino C;Kadoor A;Hosszu KK;Ramadass M;Kew RR;Kishore U;Peerschke EI;Ghebrehiwet B
通讯作者：
Ghebrehiwet B
影响因子：
7.4
作者：
Boddupalli, Chandra Sekhar;Ghosh, Sudip;Mukhopadhyay, Sangita
通讯作者：
Mukhopadhyay, Sangita
影响因子：
4.8
作者：
de Bittencourt Pasquali, Matheus Augusto;Gelain, Daniel Pens;Fonseca Moreira, Jose Claudio
通讯作者：
Fonseca Moreira, Jose Claudio
影响因子：
3.8
作者：
Kekarainen, Tuija;Montoya, Maria;Segales, Joaquim
通讯作者：
Segales, Joaquim
影响因子：
2.9
作者：
Mair KH;Sedlak C;Käser T;Pasternak A;Levast B;Gerner W;Saalmüller A;Summerfield A;Gerdts V;Wilson HL;Meurens F
通讯作者：
Meurens F