Comparative Medicine Research Institute, Yangzhou University, China; College Veterinary Medicine, Yangzhou University, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, 225009, China.
BIOEPAR, INRA, Oniris, 44307, Nantes, France.
Dev Comp Immunol. 2020 Mar;104:103555. doi: 10.1016/j.dci.2019.103555. Epub 2019 Nov 18.
As one family of pattern recognition receptors (PRRs), The C-type lectin receptors (CLRs) play a key role in the anti-fungal infection. The CLR pathway signaling is relayed by adaptor complex which comprises CARD9, BCL10 and MALT1. However, the relationship between these three adaptors has not been investigated. In this study, we isolated porcine CARD9, BCL10 and MALT1 and examined their signaling functions. The three ectopic adaptors were similarly and uniformly expressed in cytoplasm, with CARD9 inactive, BCL10 significant active, and MALT1 slightly active for downstream NF-κB signaling and gene expressions. With the three adaptors together, NF-κB signaling and gene expressions were strongly activated, however, no IFN signal was activated in any case. The signaling relationship between the adaptors were dissected, the NF-κB signaling results showed that CARD9 could inhibit both BCL10 and MALT1 activities, while BCL10 and MALT1 synergized each other particularly when moderate amount of BCL10 plus low amount of MALT1 were considered. Low amount of CARD9 could further synergized with BCL10 and MALT1, maximizing signaling activity of the adaptor complex. This study revealed the porcine CLR pathway adaptor signaling functions and their optimal collective activity, thus providing a unique insight into the porcine innate immunity.
作为模式识别受体(PRRs)的一个家族,C 型凝集素受体(CLRs)在抗真菌感染中发挥着关键作用。CLR 途径信号通过衔接复合物转导,该复合物由 CARD9、BCL10 和 MALT1 组成。然而,这三个衔接器之间的关系尚未被研究。在这项研究中,我们分离了猪的 CARD9、BCL10 和 MALT1,并检查了它们的信号功能。这三个异位衔接器在细胞质中以相似且均匀的方式表达,其中 CARD9 无活性,BCL10 显著活跃,而 MALT1 对下游 NF-κB 信号和基因表达只有轻微的活性。当这三个衔接器一起使用时,NF-κB 信号和基因表达被强烈激活,但在任何情况下都没有激活 IFN 信号。我们对衔接器之间的信号关系进行了剖析,NF-κB 信号结果表明,CARD9 可以抑制 BCL10 和 MALT1 的活性,而 BCL10 和 MALT1 则彼此协同作用,特别是当考虑到适量的 BCL10 加上少量的 MALT1 时。少量的 CARD9 可以与 BCL10 和 MALT1 进一步协同作用,使衔接子复合物的信号活性最大化。这项研究揭示了猪的 CLR 途径衔接子信号功能及其最佳的集体活性,从而为猪的先天免疫提供了独特的见解。