Roles of polymorphic cathelicidins in innate immunity of soft-shell turtle, Pelodiscus sinensis.

ABSTRACT

Cathelicidins are a class of gene-encoded immune effectors in vertebrate innate immune system. Though being extensively studied in mammals, little is known about the roles of cathelicidins in turtles, the water-dwelling vertebrates in the order Testudines. In the present study, six novel cathelicidins (Ps-CATH1-6) with different tissue and inducible expression patterns were characterized from the turtle of economic importance, Chinese soft-shell turtle (Pelodiscus sinensis). Although the structures of Ps-CATH1-6 precursors were identical with most of the other known cathelicidins, the mature peptides of Ps-CATH1-6 showed low sequence similarity with the other cathelicidins. Functional studies indicated that some of them either directly kill pathogens via inducing the permeabilization in bacterial membrane (Ps-CATH4, 6), or boost infection-resolving immunity by selectively inhibiting pro-inflammatory responses (Ps-CATH2, 4, 6) through MAPKs and NF-κB pathways. Ps-CATH2, 4, and 6, which assume the hallmark amphipathic α-helical conformations as most of the other host defense peptides, exhibit evident in vivo protection by significantly reducing the bacterial loads in bacterial infected turtles. Collectively, the discovery of novel Ps-CATHs with pleiotropic structures and functions helps elucidating the roles of cathelicidins in the Chinese softshell turtle innate immunity, and better understanding the survival strategy of Chinese softshell turtle in harsh habitat.