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European Journal of Dermatology : EJD 2008The skin continuously encounters microbial pathogens. To defend against this, cells of the epidermis and dermis have evolved several innate strategies to prevent... (Review)
Review
The skin continuously encounters microbial pathogens. To defend against this, cells of the epidermis and dermis have evolved several innate strategies to prevent infection. Antimicrobial peptides are one of the primary mechanisms used by the skin in the early stages of immune defense. In general, antimicrobial peptides have broad antibacterial activity against gram-positive and negative bacteria and also show antifungal and antiviral activity. The antimicrobial activity of most peptides occurs as a result of unique structural characteristics that enable them to disrupt the microbial membrane while leaving human cell membranes intact. However, antimicrobial peptides also act on host cells to stimulate cytokine production, cell migration, proliferation, maturation, and extracellular matrix synthesis. The production by human skin of antimicrobial peptides such as defensins and cathelicidins occurs constitutively but also greatly increases after infection, inflammation or injury. Some skin diseases show altered expression of antimicrobial peptides, partially explaining the pathophysiology of these diseases. Thus, current research suggests that understanding how antimicrobial peptides modify susceptibility to microbes, influence skin inflammation, and modify wound healing, provides greater insight into the pathophysiology of skin disorders and offers new therapeutic opportunities.
Topics: Antimicrobial Cationic Peptides; Cathelicidins; Defensins; Dermcidins; Humans; Skin; Skin Diseases
PubMed: 18086583
DOI: 10.1684/ejd.2008.0304 -
Islets 2019The gut microbiota can play a role in pancreatitis and, likely, in the development of type 1 diabetes (T1D). Anti-microbial peptides and secretory proteins are important...
The gut microbiota can play a role in pancreatitis and, likely, in the development of type 1 diabetes (T1D). Anti-microbial peptides and secretory proteins are important mediators of the innate immune response against bacteria but their expression in the human pancreas is not fully known. In this study, immunohistochemistry was used to analyze the expression of seven anti-microbial peptides (Defensin α1, α4, β1-4 and Cathelicidin) and two secretory proteins with known antimicrobial properties (REG3A and GP2) in pancreatic and duodenal biopsies from 10 non-diabetic organ donors and one organ donor that died at onset of T1D. Immunohistochemical data was compared with previously published whole-transcriptome data sets. Seven (Defensin α1, β2, β3, α4, GP2, Cathelicidin, and REG3A) host defense molecules showed positive staining patterns in most non-diabetic organ donors, whereas two (Defensin β1 and β4) were negative in all non-diabetic donors. Two molecules (Defensin α1 and GP2) were restricted to the exocrine pancreas whereas two (Defensin β3, α4) were only expressed in islet tissue. Cathelicidin, β2, and REG3A were expressed in both islets and exocrine tissue. The donor that died at onset of T1D had generally less positivity for the host defense molecules, but, notably, this pancreas was the only one where defensin β1 was found. Neither donor age, immune-cell infiltration, nor duodenal expression correlated to the pancreatic expression of host defense molecules. In conclusion, these findings could have important implications for the inflammatory processes in diabetes and pancreatitis as we find several host defense molecules expressed by the pancreatic tissue.
Topics: Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Defensins; Diabetes Mellitus, Type 1; Female; GPI-Linked Proteins; Gene Expression; Humans; Immunohistochemistry; Infant; Male; Pancreas; Pancreatitis-Associated Proteins; Tissue Donors; Young Adult
PubMed: 31242128
DOI: 10.1080/19382014.2019.1585165 -
Molecules (Basel, Switzerland) Aug 2014Plant defensins are small, cysteine-rich peptides that possess biological activity towards a broad range of organisms. Their activity is primarily directed against... (Review)
Review
Plant defensins are small, cysteine-rich peptides that possess biological activity towards a broad range of organisms. Their activity is primarily directed against fungi, but bactericidal and insecticidal actions have also been reported. The mode of action of various antifungal plant defensins has been studied extensively during the last decades and several of their fungal targets have been identified to date. This review summarizes the mechanism of action of well-characterized antifungal plant defensins, including RsAFP2, MsDef1, MtDef4, NaD1 and Psd1, and points out the variety by which antifungal plant defensins affect microbial cell viability. Furthermore, this review summarizes production routes for plant defensins, either via heterologous expression or chemical synthesis. As plant defensins are generally considered non-toxic for plant and mammalian cells, they are regarded as attractive candidates for further development into novel antimicrobial agents.
Topics: Amino Acid Motifs; Ascomycota; Defensins; Immunity, Innate; Microbial Viability; Molecular Sequence Data; Plant Diseases; Plant Proteins; Plants
PubMed: 25153857
DOI: 10.3390/molecules190812280 -
Future Microbiology Jan 2010Human neutrophil peptide alpha-defensins and human beta-defensins are small, well-characterized peptides with broad antimicrobial activities. In mixtures with microbial... (Review)
Review
Human neutrophil peptide alpha-defensins and human beta-defensins are small, well-characterized peptides with broad antimicrobial activities. In mixtures with microbial antigens, defensins attenuate proinflammatory cytokine responses by dendritic cells in culture, attenuate proinflammatory cytokine responses in the nasal fluids of exposed mice and enhance antibody responses in the serum of vaccinated mice. Although the exact mechanisms are unknown, defensins first start by binding to microbial antigens and adhesins, often attenuating toxic or inflammatory-inducing capacities. Binding is not generic; it appears to be both defensin-specific and antigen-specific with high affinities. Binding of defensins to antigens may, in turn, alter the interaction of antigens with epithelial cells and antigen-presenting cells attenuating the production of proinflammatory cytokines. The binding of defensins to antigens may also facilitate the delivery of bound antigen to antigen-presenting cells in some cases via specific receptors. These interactions enhance the immunogenicity of the bound antigen in an adjuvant-like fashion. Future research will determine the extent to which defensins can suppress early events in inflammation and enhance systemic antibody responses, a very recent and exciting concept that could be exploited to develop therapeutics to prevent or treat a variety of oral mucosal infections, particularly where inflammation plays a role in the pathogenesis of disease and its long-term sequelae.
Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents; Humans; Mice; alpha-Defensins; beta-Defensins
PubMed: 20020832
DOI: 10.2217/fmb.09.104 -
Microbiology Spectrum Aug 2023Mycobacterium abscessus, an intracellular nontuberculous mycobacterium, is considered the most pathogenic species among the group of rapidly growing mycobacteria. The...
Mycobacterium abscessus, an intracellular nontuberculous mycobacterium, is considered the most pathogenic species among the group of rapidly growing mycobacteria. The resistance of M. abscessus to the host innate response contributes to its pathogenicity in addition to several virulence factors. We have recently shown in that antimicrobial peptides (AMPs), whose production is induced by M. abscessus, are unable to control mycobacterial infection. This could be due to their inability to kill mycobacteria and/or the hidden location of the pathogen in phagocytic cells. Here, we demonstrate that the rapid internalization of M. abscessus by macrophages allows it to escape the AMP-mediated humoral response. By depleting phagocytes in AMP-deficient flies, we found that several AMPs were required for the control of extracellular M. abscessus. This was confirmed in the Tep4 opsonin-deficient flies, which we show can better control M. abscessus growth and have increased survival through overproduction of some AMPs, including Defensin. Furthermore, Defensin alone was sufficient to kill extracellular M. abscessus both and and control its infection. Collectively, our data support that Tep4-mediated opsonization of M. abscessus allows its escape and resistance toward the Defensin bactericidal action in . Mycobacterium abscessus, an opportunistic pathogen in cystic fibrosis patients, is the most pathogenic species among the fast-growing mycobacteria. How M. abscessus resists the host innate response before establishing an infection remains unclear. Using , we have recently demonstrated that M. abscessus resists the host innate response by surviving the cytotoxic lysis of the infected phagocytes and the induced antimicrobial peptides (AMPs), including Defensin. In this work, we demonstrate that M. abscessus resists the latter response by being rapidly internalized by phagocytes. Indeed, by combining and approaches, we show that Defensin is able to control extracellular M. abscessus infection through a direct bactericidal action. In conclusion, we report that M. abscessus escapes the host AMP-mediated humoral response by taking advantage of its internalization by the phagocytes.
Topics: Animals; Mycobacterium abscessus; Drosophila; Opsonization; Mycobacterium; Antimicrobial Peptides; Defensins; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents
PubMed: 37260399
DOI: 10.1128/spectrum.00777-23 -
Biomedica : Revista Del Instituto... Mar 2021It is essential to determine the interactions between viruses and mosquitoes to diminish dengue viral transmission. These interactions constitute a very complex system...
INTRODUCTION
It is essential to determine the interactions between viruses and mosquitoes to diminish dengue viral transmission. These interactions constitute a very complex system of highly regulated pathways known as the innate immune system of the mosquito, which produces antimicrobial peptides that act as effector molecules against bacterial and fungal infections. There is less information about such effects on virus infections.
OBJECTIVE
To determine the expression of two antimicrobial peptide genes, defensin A and cecropin A, in Aedes aegypti mosquitoes infected with DENV-1.
MATERIALS AND METHODS
We used the F1 generation of mosquitoes orally infected with DENV-1 and real-time PCR analysis to determine whether the defensin A and cecropin A genes played a role in controlling DENV-1 replication in Ae. aegypti. As a reference, we conducted similar experiments with the bacteria Escherichia coli.
RESULTS
Basal levels of defensin A and cecropin A mRNA were expressed in uninfected mosquitoes at different times post-blood feeding. The infected mosquitoes experienced reduced expression of these mRNA by at least eightfold when compared to uninfected control mosquitoes at all times post-infection. In contrast with the behavior of DENV-1, results showed that bacterial infection produced up-regulation of defensin and cecropin genes; however, the induction of transcripts occurred at later times (15 days).
CONCLUSION
DENV-1 virus inhibited the expression of defensin A and cecropin A genes in a wild Ae. aegypti population from Venezuela.
Topics: Aedes; Animals; Antimicrobial Cationic Peptides; Defensins; Dengue Virus
PubMed: 33761199
DOI: 10.7705/biomedica.5491 -
The Journal of Investigative Dermatology Jul 2005The skin actively contributes to host defense by mounting an innate immune response that includes the production of antimicrobial peptides. These peptides, which include... (Review)
Review
The skin actively contributes to host defense by mounting an innate immune response that includes the production of antimicrobial peptides. These peptides, which include but are not limited to the cathelicidin and defensin gene families, provide rapid, broad-spectrum defense against infection by acting as natural antibiotics and by participating in host cell processes involved in immune defense. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin. The importance of the epithelial contribution to host immunity is evident, as alterations in antimicrobial peptide expression have been associated with various pathologic processes.
Topics: Antimicrobial Cationic Peptides; Bacterial Infections; Defensins; Gene Expression Regulation; Humans; Immunity, Innate; Skin; Cathelicidins
PubMed: 15982297
DOI: 10.1111/j.0022-202X.2004.23587.x -
International Journal of Molecular... Mar 2022belongs to Dinidoridae, Hemiptera. Previous studies have indicated that contains abundant polypeptides with antibacterial and anticancer activities. Antimicrobial...
belongs to Dinidoridae, Hemiptera. Previous studies have indicated that contains abundant polypeptides with antibacterial and anticancer activities. Antimicrobial peptides (AMPs), as endogenous peptides with immune function, play an indispensable role in the process of biological development and immunity. AMPs have become one of the most potential substitutes for antibiotics due to their small molecular weight and broad-spectrum antimicrobial activity. In this study, a defensin CcDef2 from was characterized based on bioinformatics and functional analyses. The mature peptide of CcDef2 is a typical cationic peptide composed of 43 amino acid residues with five cations, and contains three intramolecular disulfide bonds and a typical cysteine-stabilized αβ motif in defensins. Phylogenetic analysis showed that CcDef2 belongs to the insect defensin family. Analysis of gene expression patterns showed that was expressed throughout developmental stages of with high levels at the nymphal stage and in adult tissues tested with the highest level in the fat body. In addition, the expression was significantly upregulated in adults infected by bacteria. After expressed in BL21(DE3) and renatured, the recombinant CcDef2 showed a significant antibacterial effect on three kinds of Gram-positive bacteria. These results indicate that CcDef2 is an excellent antibacterial peptide and a highly effective immune effector in the innate immunity of . This study provides a foundation for further understanding the function of and developing new antimicrobial drugs.
Topics: Amino Acid Sequence; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Defensins; Heteroptera; Peptides; Phylogeny
PubMed: 35269935
DOI: 10.3390/ijms23052789 -
Antimicrobial Agents and Chemotherapy Mar 2022Severe illness caused by coronavirus disease 2019 (COVID-19) is characterized by an overexuberant inflammatory response resulting in acute respiratory distress syndrome...
Severe illness caused by coronavirus disease 2019 (COVID-19) is characterized by an overexuberant inflammatory response resulting in acute respiratory distress syndrome (ARDS) and progressive respiratory failure (A. Gupta, M. V. Madhavan, K. Sehgal, N. Nair, et al., Nat Med 26:1017-1032, 2020, https://doi.org/10.1038/s41591-020-0968-3). Rhesus theta (θ) defensin-1 (RTD-1) is a macrocyclic host defense peptide exhibiting antimicrobial and immunomodulatory activities. RTD-1 treatment significantly improved survival in murine models of a severe acute respiratory syndrome (SARS-CoV-1) and endotoxin-induced acute lung injury (ALI) (C. L. Wohlford-Lenane, D. K. Meyerholz, S. Perlman, H. Zhou, et al., J Virol 83:11385-11390, 2009, https://doi.org/10.1128/JVI.01363-09; J. G. Jayne, T. J. Bensman, J. B. Schaal, A. Y. J. Park, et al., Am J Respir Cell Mol Biol 58:310-319, 2018, https://doi.org/10.1165/rcmb.2016-0428OC). This investigation aimed to characterize the preclinical pharmacokinetics (PK) and safety of intravenous (i.v.) RTD-1. Based on the lack of adverse findings, the no observed adverse effect level (NOAEL) was established at 10 mg/kg/day in rats and 15 mg/kg/day in monkeys. Analysis of single ascending dose studies in both species revealed greater-than-dose-proportional increases in the area under the curve extrapolated to infinity (AUC) (e.g., 8-fold increase from 5 mg/kg to 20 mg/kg in rats) suggestive of nonlinear PK. The volume of distribution at steady state () ranged between 550 and 1,461 mL/kg, indicating extensive tissue distribution, which was validated in a biodistribution study of [C]RTD-1 in rats. Based on interspecies allometric scaling, the predicted human clearance and are 6.48 L/h and 28.0 L, respectively, for an adult (70 kg). To achieve plasma exposures associated with therapeutic efficacy established in a murine model of ALI, the estimated human equivalent dose (HED) is between 0.36 and 0.83 mg/kg/day. The excellent safety profile demonstrated in these studies and the efficacy observed in the murine models support the clinical investigation of RTD-1 for treatment of COVID-19 or other pulmonary inflammatory diseases.
Topics: Acute Lung Injury; Animals; Defensins; Mice; Rats; Tissue Distribution; COVID-19 Drug Treatment
PubMed: 35041507
DOI: 10.1128/aac.02125-21 -
Infectious Diseases of Poverty Jun 2022Ticks are hematophagous parasites that transmit an extensive range of pathogens to their vertebrate hosts. Ticks can destroy invading microorganisms or alleviate... (Review)
Review
BACKGROUND
Ticks are hematophagous parasites that transmit an extensive range of pathogens to their vertebrate hosts. Ticks can destroy invading microorganisms or alleviate infection via their rudimentary but orchestrated innate immune system. Antimicrobial peptides (AMPs) are important components of tick innate immunity. Among these humoral effector molecules, defensins are well-studied and widely identified in various species of Ixodidae (hard ticks) and Argasidae (soft ticks). This review was aimed at presenting the characterization of tick defensins from structure-based taxonomic status to antimicrobial function.
MAIN TEXT
All published papers written in English from 2001 to May 2022 were searched through PubMed and Web of Science databases with the combination of relevant terms on tick defensins. Reports on identification and characterization of tick defensins were included. Of the 329 entries retrieved, 57 articles were finally eligible for our scoping review. Tick defensins mainly belong to the antibacterial ancient invertebrate-type defensins of the cis-defensins superfamily. They are generally small, cationic, and amphipathic, with six cysteine residues forming three intra-molecular disulfide bonds. Tick defensins primarily target membranes of a variety of pathogens, including Gram-positive and Gram-negative bacteria, fungi, viruses, and protozoa. Since tick defensins have a high degree of variability, we summarize their common biological properties and enumerate representative peptides. Along with the various and potent antimicrobial activities, the role of tick defensins in determining vector competence is discussed.
CONCLUSIONS
Due to their broad-spectrum antimicrobial activities, tick defensins are considered novel candidates or targets for controlling infectious diseases.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Peptides; Defensins; Gram-Negative Bacteria; Gram-Positive Bacteria; Ixodidae; Ticks
PubMed: 35725522
DOI: 10.1186/s40249-022-00996-8