defensins
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Antimicrobial peptides are ubiquitous components of eukaryotic innate immunity. Defensins are a well-known family of antimicrobial peptides, widely distributed in ticks, insects, plants and mammals, showing activity against bacteria, viruses, fungi, yeast and protozoan parasites. Ixodes ricinus is the most common tick species in Europe and is a vector of pathogens affecting human and animal health. Recently, six defensins (including two isoforms) were identified in I. ricinus. We investigated the evolution of the antimicrobial activity of I. ricinus defensins. Among the five unique defensins, only DefMT3, DefMT5 and DefMT6 showed in vitro antimicrobial activity. Each defensin was active against rather distantly-related bacteria (P < 0.05), significantly among Gram-negative species (P < 0.0001). These three defensins represent different clades within the family of tick defensins, suggesting that the last common ancestor of tick defensins may have had comparable antimicrobial activity. Differences in electrostatic potential, and amino acid substitutions in the β-hairpin and the loop bridging the α-helix and β-sheet may affect the antimicrobial activity in DefMT2 and DefMT7, which needs to be addressed. Additionally, the antimicrobial activity of the γ-core motif of selected defensins (DefMT3, DefMT6, and DefMT7) was also tested. Interestingly, compared to full length peptides, the γ-core motifs of these defensins were effective against less species of bacteria. However, the antifungal activity of the γ-core was higher than full peptides. Our results broaden the scope of research in the field of antimicrobial peptides highlighting the overlooked ability of arthropod defensins to act against distantly-related microorganisms.
- MeSH
- aminokyselinové motivy MeSH
- bakteriální infekce imunologie MeSH
- biologická evoluce MeSH
- defensiny genetika metabolismus MeSH
- druhová specificita MeSH
- hmyzí proteiny genetika metabolismus MeSH
- interakce hostitele a patogenu MeSH
- klíště * MeSH
- kultivované buňky MeSH
- mykózy imunologie MeSH
- přirozená imunita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The red flour beetle Tribolium castaneum is a destructive insect pest of stored food and feed products, and a model organism for development, evolutionary biology and immunity. The insect innate immune system includes antimicrobial peptides (AMPs) with a wide spectrum of targets including viruses, bacteria, fungi and parasites. Defensins are an evolutionarily-conserved class of AMPs and a potential new source of antimicrobial agents. In this context, we report the antimicrobial activity, phylogenetic and structural properties of three T. castaneum defensins (Def1, Def2 and Def3) and their relevance in the immunity of T. castaneum against bacterial pathogens. All three recombinant defensins showed bactericidal activity against Micrococcus luteus and Bacillus thuringiensis serovar tolworthi, but only Def1 and Def2 showed a bacteriostatic effect against Staphylococcus epidermidis. None of the defensins showed activity against the Gram-negative bacteria Escherichia coli and Pseudomonas entomophila or against the yeast Saccharomyces cerevisiae. All three defensins were transcriptionally upregulated following a bacterial challenge, suggesting a key role in the immunity of T. castaneum against bacterial pathogens. Phylogenetic analysis showed that defensins from T. castaneum, mealworms, Udo longhorn beetle and houseflies cluster within a well-defined clade of insect defensins. We conclude that T. castaneum defensins are primarily active against Gram-positive bacteria and that other AMPs may play a more prominent role against Gram-negative species.
- MeSH
- defensiny fyziologie MeSH
- fylogeneze MeSH
- grampozitivní bakterie imunologie MeSH
- hmyzí proteiny fyziologie MeSH
- přirozená imunita MeSH
- regulace genové exprese MeSH
- Tribolium imunologie MeSH
- výpočetní biologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Despite the importance of ticks as vectors of disease very little is known about their immune system. Antimicrobial peptides, including defensins (phylogenetically ancient antibacterial peptides) are major components of innate immunity in ticks that have been shown to provide protection against gram-negative and gram-positive bacteria, fungi, viruses and protozoan parasites. With the aim of studying the evolution of the genes involved in tick defense, we identified the preprodefensin genes from four Ornithodoros tick species (O. papillipes: isoforms A, B, and D; O. tartakovskyi and O. puertoricensis: isoforms A and B; O. rostratus: isoform A) and from two Dermacentor tick species (D. reticulatus and D. marginatus: one isoform) not previously described. Phylogenetic analyses revealed that Ornithodoros defensin isoforms (A, B, C, and D) form 4 separate clades, while hard tick defensins are divided into several branches based on particular tick species.
Malaria is a mosquito-borne disease affecting millions of people mainly in Sub-Saharan Africa, Asia and some South American countries. Drug resistance to first-line antimalarial drugs (e.g. chloroquine, sulfadoxine-pyrimethamine and artemisinin) is a major constrain in malaria control. Antimicrobial peptides (AMPs) have shown promising results in controlling Plasmodium spp. parasitemia in in vitro and in vivo models of infection. Defensins are AMPs that act primarily by disrupting the integrity of cell membranes of invasive microbes. We previously showed that defensins from the tick Ixodes ricinus inhibited significantly the growth of P. falciparum in vitro, a property that was conserved during evolution. Here, we tested the activity of three I. ricinus defensins against P. chabaudi in mice. A single dose of defensin (120 μl of 1 mg/ml solution) was administered intravenously to P. chabaudi-infected mice, and the parasitemia was followed for 24 h post-treatment. Defensin treatment inhibited significantly the replication (measured as increases in parasitemia) of P. chabaudi after 1 h and 12 h of treatment. Furthermore, defensin injection was not associated with toxicity. These results agreed with the previous report of antiplasmodial activity of tick defensins against P. falciparum in vitro and justify further studies for the use of tick defensins to control malaria.
- MeSH
- antimalarika aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- defensiny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- intravenózní podání MeSH
- klíště chemie MeSH
- malárie farmakoterapie parazitologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- parazitemie farmakoterapie parazitologie MeSH
- Plasmodium účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lyme arthritis, one of the possible late manifestations of Lyme borreliosis, predominantly affects the supporting joints and in adults most often occurs in the form of monoarthritis of the knee. Early diagnosis is based on clinical findings and serology. PCR detection of Borrelia in synovial fluid has become an integral part of the laboratory testing algorithm. The clinical presentation and inflammatory markers in Lyme arthritis can resemble septic arthritis. Determining the levels of alpha-defensins (human neutrophil peptide (HNP 1-3)) in synovial fluid by liquid chromatography is a highly sensitive method revealing the presence of inflammatory process. Between 2020 and 2022, we examined eleven patients with Lyme arthritis of the knee. We measured levels of HNP 1-3 from synovial fluid by HPLC in patients, and we compared it with the corresponding C-reactive protein (CRP) levels in paired serum samples. In patients diagnosed with Lyme arthritis, HNP 1-3 levels in synovial fluid ranged from 2.5 to 261 mg/L, with a median of 46.5 mg/L. Average serum CRP was 43 mg/L. The results show that elevated HNP 1-3 can be consistent with not only septic arthritis or systemic disease, but also with Lyme arthritis, especially in patients with negative culture and 16S PCR from synovial fluid. Final diagnosis must be verified by examination for anti-Borrelia antibodies from serum and synovial fluid. The aim of this work is to introduce an HPLC method for the determination of alpha-defensins as one of the possible diagnostic markers.
- MeSH
- alfa-defensiny * metabolismus analýza MeSH
- biologické markery * analýza MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- infekční artritida mikrobiologie diagnóza imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc * diagnóza imunologie mikrobiologie MeSH
- senioři MeSH
- synoviální tekutina * chemie imunologie mikrobiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The gut is the biggest immune organ in the body that encloses commensal microbiota which aids in food digestion. Paneth cells, positioned at the frontline of host-microbiota interphase, can modulate the composition of microbiota. Paneth cells achieve this via the delivery of microbicidal substances, among which enteric α-defensins play the primary role. If microbiota is dysregulated, it can impact the function of the local mucosal immune system. Importantly, this system is also exposed to an enormous number of antigens which are derived from the gut-resident microbiota and processed food, and may potentially trigger undesirable local inflammatory responses. To understand the intricate regulations and liaisons between Paneth cells, microbiota and the immune system in this intestinal-specific setting, one must consider their mode of interaction in a wider context of regulatory processes which impose immune tolerance not only to self, but also to microbiota and food-derived antigens. These include, but are not limited to, tolerogenic mechanisms of central tolerance in the thymus and peripheral tolerance in the secondary lymphoid organs, and the intestine itself. Defects in these processes can compromise homeostasis in the intestinal mucosal immunity. In this review, which is focused on tolerance to intestinal antigens and its relevance for the pathogenesis of gut immune diseases, we provide an outline of such multilayered immune control mechanisms and highlight functional links that underpin their cooperative nature.
- MeSH
- alfa-defensiny biosyntéza imunologie farmakologie MeSH
- centrální tolerance MeSH
- dysbióza imunologie mikrobiologie prevence a kontrola MeSH
- exprese genu imunologie MeSH
- gastrointestinální trakt účinky léků imunologie mikrobiologie MeSH
- homeostáza imunologie MeSH
- lidé MeSH
- Panethovy buňky účinky léků imunologie mikrobiologie MeSH
- periferní tolerance * MeSH
- regulační T-lymfocyty imunologie mikrobiologie MeSH
- slizniční imunita účinky léků MeSH
- střevní mikroflóra imunologie MeSH
- symbióza imunologie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- antifungální látky chemie farmakologie MeSH
- Candida albicans účinky léků MeSH
- defensiny chemie genetika imunologie MeSH
- Fusarium účinky léků MeSH
- fylogeneze MeSH
- gramnegativní bakterie účinky léků MeSH
- grampozitivní bakterie účinky léků MeSH
- klíště genetika imunologie MeSH
- proteiny členovců chemie genetika imunologie MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Austrálie MeSH
AIMS: The study aims were to verify the serum (S) and synovial fluid (SF) reference intervals (RIs) for human neutrophil defensins (HNP1-3); measure S and SF defensin concentrations in different types of SF, including non-inflammatory, inflammatory non-pyogenic, inflammatory pyogenic, and hemorrhagic; and to compare the HNP1-3 concentrations in SF and S with those of other inflammatory biomarkers. METHODS: SF and S samples were collected from 92 patients. HNP1-3 concentrations were determined using enzyme-linked immunosorbent assays; glucose, lactate, interleukin-6, and procalcitonin using an automatic analyzer; and presepsin using a Pathfast system. There were 61 non-inflammatory, 11 inflammatory non-pyogenic, 11 inflammatory pyogenic, and 9 hemorrhagic SF. Non-inflammatory SF was divided into non-inflammatory normal and non-inflammatory osteoarthritis. The former was used to estimate the HNP1-3 RI in SF and S. RESULTS: The estimated HNP1-3 RIs of SF and S were 12.47-437.42 mg/L and 5.45-44.75 μg/L, respectively. HNP1-3 differed significantly between S and SF and individual groups of SF (P<0.001 and P=0.001, respectively). There were significant relationships between SF HNP1-3 and S HNP1-3 (P<0.001), S C-reactive protein (P<0.001), and S interleukin-6 (P=0.007), and between SF HNP1-3 and SF C-reactive protein (P=0.004) and SF interleukin-6 (P<0.001). The highest kappa coefficient was between SF HNP1-3 and SF interleukin-6 (κ=0.507). CONCLUSIONS: We validated the SF HNP1-3 diagnostic kit and demonstrated that SF and S HNP1-3 are promising biomarkers for distinguishing inflammatory from non-inflammatory joint diseases.
