Abstract
Chicken NK-lysin (cNK-lysin), the chicken homologue of human granulysin, is a cationic amphiphilic antimicrobial peptide (AMP) that is produced by cytotoxic T cells and natural killer cells. We previously demonstrated that cNK-lysin and cNK-2, a synthetic peptide incorporating the core α-helical region of cNK-lysin, have antimicrobial activity against apicomplexan parasites such as Eimeria spp., via membrane disruption. In addition to the antimicrobial activity of AMPs, the immunomodulatory activity of AMPs mediated by their interactions with host cells is increasingly recognized. Thus, in this study, we investigated whether cNK-lysin derived peptides modulate the immune response in the chicken macrophage cell line HD11 and in chicken primary monocytes by evaluating the induction of chemokines, anti-inflammatory properties, and activation of signalling pathways. cNK-2 induced the expression of CCL4, CCL5 and interleukin(IL)-1β in HD11 cells and CCL4 and CCL5 in primary monocytes. We also determined that cNK-2 suppresses the lipopolysaccharide-induced inflammatory response by abrogating IL-1β expression. The immunomodulatory activity of cNK-2 involves the mitogen-activated protein kinases-mediated signalling pathway, including p38, extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinases, as well as the internalization of cNK-2 into the cells. These results indicate that cNK-2 is a potential novel immunomodulating agent rather than an antimicrobial agent.
Highlights
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[1]
Studies of cationic AMPs have focused on their antimicrobial functions against diverse microorganisms as part of efforts to develop alternative treatments for multidrug-resistant bacteria[18]
We previously noted the antimicrobial activity of cNK-lysin as well as its derivatives[11,12] and demonstrated that cNK-lysin peptides are among the few cationic peptides that kill bacteria and parasites through a direct interaction that results in disruption of the plasma membrane
Summary
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[1]. The direct activity of cationic AMPs towards the microbial membrane is dependent on physiological conditions, such as salt and serum[3]. The immunomodulatory activity of cationic AMPs varies depending on the cell type. Because of their ability to modulate the immune response, it has been proposed that cationic AMPs be called host defence peptides (HDPs). We demonstrated that cNK-2 has immunomodulatory properties as an HDP, including inducing chemokines/cytokines, an anti-inflammatory response, signalling pathway activation and internalization into cells. Not all of our findings are consistent with previously studied cationic AMPs or HDPs, and this study provides advanced insight on how the chicken immune response is modulated by peptides
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