The signaling relations between three adaptors of porcine C-type lectin receptor pathway

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.