"Host defense peptides with anti-microbial and immunomodulatory activities as antibiotic alternatives"

Authors: KIM, WOOHYUN - US Department Of Agriculture (USDA); Lillehoj, Hyun

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/1/2019
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: With the increasing emergence of antibiotic-resistant pathogens, antimicrobial peptides (AMPs) have been studied as alternatives to antibiotics based on their broad spectrum of bactericidal activity and selectivity. Cationic antimicrobial peptides are highly conserved in all organisms and are effective against many bacteria, including multidrug-resistant bacterial strains, by disrupting the bacterial membrane based on their cationic nature. However, the direct activity of cationic AMPs towards the microbial membrane is dependent on physiological conditions such as salt and serum. Increasing evidence indicates that direct microbial killing may not be the primary role of cationic AMPs in the body, and efforts to determine the role of cationic AMPs have focused on the immunomodulatory properties of cationic AMPs. The immunomodulatory activity of cationic AMPs is complex and includes anti-infective immune modulation such as the induction of chemokines and cytokines, pro/anti-inflammatory activity, direct chemotaxis, wound healing, angiogenesis, apoptotic activity and adjuvant activity. The immunomodulatory activity of cationic AMPs also varies depending on the cell type. Because of their ability to modulate the immune response, cationic AMPs are called host defense peptides (HDPs). Chicken NK-lysin (cNK-lysin) is a homologue of human granulysin which is found in the cytolytic granules located in human natural killer and cytotoxic T lymphocytes. It was previously demonstrated that cNK-lysin is hugely expressed in Eimeria-infected intestinal lymphocytes, suggesting a role in parasite infection. Subsequent studies have shown that cNK-lysin and cNK-2, the core a-helical region of cNK-lysin, can kill Eimeria sporozoites by disrupting the parasitic membrane. Interestingly, cNK-2 exhibits higher antimicrobial activity than the original peptide and even melittin indicating that the modification of the natural sequence can improve efficiency. In mammals, granulysin acts as an immunomodulatory peptide by serving as a chemoattractant for lymphocytes and modulating the expression of chemokines and cytokines. The present study demonstrates that cNK-2 has immunomodulatory properties as an HDP, including inducing chemokines/cytokines, an anti-inflammatory response, signaling pathway activation and internalization into chicken cells. By contrast, the antimicrobial effects of cNK-2 were reduced under physiological salt conditions. The responses of HD11 cells and primary monocytes to cNK-2 were also studied to understand the role of cNK-2 in innate immunity. The findings presented here provide advanced insight on how the chicken immune response is modulated by HDPs.