Naturally Occurring Antimicrobial Peptide OH-CATH30 Selectively Regulates the Innate Immune Response To Protect against Sepsis

Sepsis, which is a systemic inflammatory response that follows a bacterial infection, has a high mortality rate and limited therapeutic options. Here we show that the antimicrobial peptide OH-CATH30, which naturally occurs in snake, selectively regulates the innate immune response to protect mice from lethal sepsis. The administration of OH-CATH30 significantly improves the survival rate of mice infected by antibiotic-susceptible and -resistant pathogens, including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. OH-CATH30 selectively up-regulates the production of chemokines and cytokines without harmful immune response. Recruitment of monocytes, macrophages, and neutrophils to the infection site is pivotal to the protective capacity of OH-CATH30. Furthermore, the alternative activation of the innate immune response by OH-CATH30 depends on p38 mitogen-activated protein kinase signaling. Taken together, our study demonstrates that OH-CATH30, a naturally occurring antimicrobial peptide,...