DISK ABALONE IRAK4 INVOLVED IN POTENT IMMUNE RESPONSES DURING PATHOGENIC STRESS, BUT IMPAIRS MYD88 MEDIATED NF-?B ACTIVITY

Disk abalone (Haliotis discus discus) is one of the commercially important marine gastropod species in eastern Asia including Korea. However, overall abalone production has been markedly affected by mass mortalities due to the pathogenic infections. Invertebrates, including abalone are totally depend on innate immune system, because they lack well developed adaptive immunity. Therefore comprehensive study on abalone innate immunity is mandatory to establish novel disease management strategies. In present study, Interleukin 1 receptor associated kinase 4 (IRAK4), a critical member of Myeloid differentiate primary response factor 88 (MyD88) dependent Toll like receptor (TLR) signal transduction pathway was identified from disk abalone (designated as AbIRAK4) and functionally characterized.

The AbIRAK4 comprised with typical IKK structural features including N-terminal death domain and C-terminal protein kinase domain, similar to its mammalian counterparts. Expressional analysis revealed that AbIRAK4, mRNA constitutively expressed at all the early embryonic stages of disk abalone analyzed. In the un-challenged abalones AbIRAK4 was ubiquitously expressed in all the tissues analyzed with the highest expression levels in the hemocytes. Significantly up-regulated mRNA expression of AbIRAK4 was detected in hemocytes and gills after challenge with Gram-negative Vibrio parahemolyticus, Gram-positive Listeria monocytogenes, viral hemorrhagic septicemia virus (VHSV), LPS and poly I:C. Overexpression of AbIRAK4 in HEK293T cells unable to induce the activities of NF-κB and AP-1 responsive reporters. Interestingly, AbIRAK4 significantly diminished abalone MyD88-2 and MyD88-X mediated activation of NF-κB and AP-1 responsive reporters in mammalian cells. Collectively, these findings suggest that AbIRAK4 is evolutionary conserved in invertebrates and actively involved in eliciting an early innate immune responses. Although, AbIRAK4 is mediating MyD88 dependent TLR signaling, it functions in different way compared to that in mammals.