Diversity, immunoregulatory action and structure-activity relationship of green sea turtle cathelicidins.

Cathelicidins are a family of gene-encoded immune effectors in vertebrate innate immunity. Here, we reported the diversity and biological activity of cathelicidins in green sea turtle, a marine reptile species known for long lifespan and disease resistance. Four novel cathelicidins (Cm-CATH1-4) were identified from green sea turtle. All of them, especially Cm-CATH2, exhibited potent, broad-spectrum and rapid bactericidal and anti-biofilm activities by inducing the disruption of cell membrane integrity. Additionally, Cm-CATH2 effectively induced the macrophages/monocytes and neutrophils trafficking to the infection site, and inhibited the LPS-induced production of inflammatory cytokines, by blocking TLR4/MD2 complex and the downstream signaling pathway activation. In mouse peritonitis and pneumonia models, Cm-CATH2 exhibited evident protection against drug-resistant bacterial infections. Taken together, the diverse structures and functions of Cm-CATHs indicated their pleiotropic role in innate immunity of green sea turtle, and the potent antimicrobial, anti-biofilm and immunomodulatory properties make them ideal candidates for the development of novel anti-infective drugs. Image 1 • Four cathelicidins were identified from Green Sea Turtle (Chelonia mydas). • Expression of Cm-CATHs is constitutional, and inducible in response to bacterial challenge in vivo. • Cm-CATH2 directly kill pathogens via inducing the permeabilization in membrane. • Acting through MAPKs and NF-κB, Cm-CATH2 can boost infection-resolving innate immunity. • Cm-CATHs exhibit evident in vivo protections by significantly reducing the bacterial loads in turtles. [ABSTRACT FROM AUTHOR]