29
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      NKLP27: A Teleost NK-Lysin Peptide that Modulates Immune Response, Induces Degradation of Bacterial DNA, and Inhibits Bacterial and Viral Infection

      research-article
      1 , 2 , 1 , 4 , 1 , 3 , *
      PLoS ONE
      Public Library of Science

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          NK-lysin is an antimicrobial protein produced by cytotoxic T lymphocytes and natural killer cells. In this study, we examined the biological property of a peptide, NKLP27, derived from tongue sole ( Cynoglossus semilaevis) NK-lysin. NKLP27 is composed of 27 amino acids and shares little sequence identity with known NK-lysin peptides. NKLP27 possesses bactericidal activity against both Gram-negative and Gram-positive bacteria including common aquaculture pathogens. The bactericidal activity of NKLP27 was dependent on the C-terminal five residues, deletion of which dramatically reduced the activity of NKLP27. During its interaction with the target bacterial cells, NKLP27 destroyed cell membrane integrity, penetrated into the cytoplasm, and induced degradation of genomic DNA. In vivo study showed that administration of tongue sole with NKLP27 before bacterial and viral infection significantly reduced pathogen dissemination and replication in tissues. Further study revealed that fish administered with NKLP27 exhibited significantly upregulated expression of the immune genes including those that are known to be involved in antibacterial and antiviral defense. These results indicate that NKLP27 is a novel antimicrobial against bacterial and viral pathogens, and that the observed effect of NKLP27 on bacterial DNA and host gene expression adds new insights to the action mechanism of fish antimicrobial peptides.

          Related collections

          Most cited references46

          • Record: found
          • Abstract: found
          • Article: not found

          The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses.

          The role of LL-37, a human cationic antimicrobial peptide, in the immune system is not yet clearly understood. It is a widely expressed peptide that can be up-regulated during an immune response. In this report, we demonstrate that LL-37 is a potent antisepsis agent with the ability to inhibit macrophage stimulation by bacterial components such as LPS, lipoteichoic acid, and noncapped lipoarabinomannan. We also demonstrate that LL-37 protects mice against lethal endotoxemia. In addition to preventing macrophage activation by bacterial components, we hypothesized the LL-37 may also have direct effects on macrophage function. We therefore used gene expression profiling to identify macrophage functions that might be modulated by LL-37. These studies revealed that LL-37 directly up-regulates 29 genes and down-regulated another 20 genes. Among the genes predicted to be up-regulated by LL-37 were those encoding chemokines and chemokine receptors. Consistent with this, LL-37 up-regulated the expression of chemokines in macrophages and the mouse lung (monocyte chemoattractant protein 1), human A549 epithelial cells (IL-8), and whole human blood (monocyte chemoattractant protein 1 and IL-8), without stimulating the proinflammatory cytokine, TNFalpha. LL-37 also up-regulated the chemokine receptors CXCR-4, CCR2, and IL-8RB. These findings indicate that LL-37 may contribute to the immune response by limiting the damage caused by bacterial products and by recruiting immune cells to the site of infection so that they can clear the infection.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA

            Indolicidin, a l3-residue antimicrobial peptide-amide, which is unusually rich in tryptophan and proline, is isolated from the cytoplasmic granules of bovine neutrophils. In this study, the structures of indolicidin in 50% D3-trifluoroethanol and in the absence and presence of SDS and D38-dodecylphosphocholine were determined using NMR spectroscopy. Multiple conformations were found and were shown to be due to different combinations of contact between the two WPW motifs. Although indolicidin is bactericidal and able to permeabilize bacterial membranes, it does not lead to cell wall lysis, showing that there is more than one mechanism of antimicrobial action. The structure of indolicidin in aqueous solution was a globular and amphipathic conformation, differing from the wedge shape adopted in lipid micelles, and these two structures were predicted to have different functions. Indolicidin, which is known to inhibit DNA synthesis and induce filamentation of bacteria, was shown to bind DNA in gel retardation and fluorescence quenching experiments. Further investigations using surface plasmon resonance confirmed the DNA-binding ability and showed the sequence preference of indolicidin. Based on our biophysical studies and previous results, we present a diagram illustrating the DNA-binding mechanism of the antimicrobial action of indolicidin and explaining the roles of the peptide when interacting with lipid bilayers at different concentrations.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Antimicrobial peptides.

              Antimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum antimicrobial activity against bacteria, viruses, and fungi. These evolutionarily conserved peptides are usually positively charged and have both a hydrophobic and hydrophilic side that enables the molecule to be soluble in aqueous environments yet also enter lipid-rich membranes. Once in a target microbial membrane, the peptide kills target cells through diverse mechanisms. Cathelicidins and defensins are major groups of epidermal AMPs. Decreased levels of these peptides have been noted for patients with atopic dermatitis and Kostmann's syndrome, a congenital neutropenia. In addition to important antimicrobial properties, growing evidence indicates that AMPs alter the host immune response through receptor-dependent interactions. AMPs have been shown to be important in such diverse functions as angiogenesis, wound healing, and chemotaxis. As our knowledge of AMP biology expands, the precise role and relevance of these peptides will be better elucidated.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                2 September 2014
                : 9
                : 9
                : e106543
                Affiliations
                [1 ]Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China
                [2 ]College of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, China
                [3 ]Collaborative Innovation Center of Deep Sea Biology, Zhejiang University, Hangzhou, China
                [4 ]Graduate University of the Chinese Academy of Sciences, Beijing, China
                Friedrich-Loeffler Institut, Germany
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LS MZ. Performed the experiments: MZ MFL. Analyzed the data: MZ MFL. Contributed reagents/materials/analysis tools: MFL MZ. Contributed to the writing of the manuscript: MZ LS.

                Article
                PONE-D-14-18969
                10.1371/journal.pone.0106543
                4152322
                25180858
                036f28dc-f77f-43aa-af1c-eb388896e22e
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 April 2014
                : 6 August 2014
                Page count
                Pages: 9
                Funding
                This work was supported by the grants of the National Natural Science Foundation of China (31101925), the National Basic Research Program of China (2012CB114406), and the Taishan Scholar Program of Shandong Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Infectious Disease Immunology
                Veterinary Science
                Veterinary Medicine
                Veterinary Immunology
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article