Escherichia coli A0 34/86 (EcO83) is a probiotic strain used in newborns to prevent nosocomial infections and diarrhoea. This bacterium stimulates both pro- and anti-inflammatory cytokine production and its intranasal administration reduces allergic airway inflammation in mice. Despite its benefits, there are concerns about the use of live probiotic bacteria due to potential systemic infections and gene transfer. Extracellular vesicles (EVs) derived from EcO83 (EcO83-EVs) might offer a safer alternative to live bacteria. This study characterizes EcO83-EVs and investigates their interaction with host cells, highlighting their potential as postbiotic therapeutics. EcO83-EVs were isolated, purified, and characterised following the Minimal Information of Studies of Extracellular Vesicles (MISEV) guidelines. Ex vivo studies conducted in human nasal epithelial cells showed that EcO83-EVs increased the expression of proteins linked to oxidative stress and inflammation, indicating an effective interaction between EVs and the host cells. Further in vivo studies in mice demonstrated that EcO83-EVs interact with nasal-associated lymphoid tissue, are internalised by airway macrophages, and stimulate neutrophil recruitment in the lung. Mechanistically, EcO83-EVs activate the NF-κΒ signalling pathway, resulting in the nitric oxide production. EcO83-EVs demonstrate significant potential as a postbiotic alternative to live bacteria, offering a safer option for therapeutic applications. Further research is required to explore their clinical use, particularly in mucosal vaccination and targeted immunotherapy strategies.
- MeSH
- aplikace intranazální * MeSH
- epitelové buňky metabolismus MeSH
- Escherichia coli * metabolismus MeSH
- extracelulární vezikuly * metabolismus MeSH
- lidé MeSH
- lymfoidní tkáň metabolismus MeSH
- makrofágy metabolismus MeSH
- myši MeSH
- NF-kappa B metabolismus MeSH
- oxidační stres MeSH
- plíce mikrobiologie metabolismus MeSH
- probiotika * aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The domestic cat (Felis catus) is an important companion animal and is used as a large animal model for human disease. However, the comprehensive study of adaptive immunity in this species is hampered by the lack of data on lymphocyte antigen receptor genes and usage. The objectives of this study were to annotate the feline T cell receptor (TR) loci and to characterize the expressed repertoire in lymphoid organs of normal cats using high-throughput sequencing. RESULTS: The Felis catus TRG locus contains 30 genes: 12 TRGV, 12 TRGJ and 6 TRGC, the TRB locus contains 48 genes: 33 TRBV, 2 TRBD, 11 TRBJ, 2 TRBC, the TRD locus contains 19 genes: 11 TRDV, 2 TRDD, 5 TRDJ, 1 TRDC, and the TRA locus contains 127 genes: 62 TRAV, 64 TRAJ, 1 TRAC. Functional feline V genes form monophyletic clades with their orthologs, and clustering of multimember subgroups frequently occurs in V genes located at the 5' end of TR loci. Recombination signal (RS) sequences of the heptamer and nonamer of functional V and J genes are highly conserved. Analysis of the TRG expressed repertoire showed preferential intra-cassette over inter-cassette rearrangements and dominant usage of the TRGV2-1 and TRGJ1-2 genes. The usage of TRBV genes showed minor bias but TRBJ genes of the second J-C-cluster were more commonly rearranged than TRBJ genes of the first cluster. The TRA/TRD V genes almost exclusively rearranged to J genes within their locus. The TRAV/TRAJ gene usage was relatively balanced while the TRD repertoire was dominated by TRDJ3. CONCLUSIONS: This is the first description of all TR loci in the cat. The genomic organization of feline TR loci was similar to that of previously described jawed vertebrates (gnathostomata) and is compatible with the birth-and-death model of evolution. The large-scale characterization of feline TR genes provides comprehensive baseline data on immune repertoires in healthy cats and will facilitate the development of improved reagents for the diagnosis of lymphoproliferative diseases in cats. In addition, these data might benefit studies using cats as a large animal model for human disease.
- MeSH
- adaptivní imunita genetika MeSH
- fylogeneze MeSH
- genetické lokusy genetika MeSH
- genomika metody MeSH
- kočky genetika imunologie MeSH
- lidé MeSH
- lymfoidní tkáň metabolismus MeSH
- receptory antigenů T-buněk klasifikace genetika MeSH
- sekvence aminokyselin MeSH
- sekvenční homologie aminokyselin MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- zvířata MeSH
- Check Tag
- kočky genetika imunologie MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The proliferation, differentiation and function of immune cells in vertebrates, as well as in the invertebrates, is regulated by distinct signalling pathways and crosstalk with systemic and cellular metabolism. We have identified the Lime gene (Linking Immunity and Metabolism, CG18446) as one such connecting factor, linking hemocyte development with systemic metabolism in Drosophila. Lime is expressed in larval plasmatocytes and the fat body and regulates immune cell type and number by influencing the size of hemocyte progenitor populations in the lymph gland and in circulation. Lime mutant larvae exhibit low levels of glycogen and trehalose energy reserves and they develop low number of hemocytes. The low number of hemocytes in Lime mutants can be rescued by Lime overexpression in the fat body. It is well known that immune cell metabolism is tightly regulated with the progress of infection and it must be supported by systemic metabolic changes. Here we demonstrate that Lime mutants fails to induce such systemic metabolic changes essential for the larval immune response. Indeed, Lime mutants are not able to sustain high numbers of circulating hemocytes and are compromised in the number of lamellocytes produced during immune system challenge, using a parasitic wasp infection model. We therefore propose the Lime gene as a novel functional link between systemic metabolism and Drosophila immunity.
- MeSH
- buněčná diferenciace MeSH
- Drosophila melanogaster imunologie metabolismus MeSH
- energetický metabolismus MeSH
- hemocyty cytologie metabolismus MeSH
- imunita * MeSH
- jaderné proteiny metabolismus MeSH
- larva metabolismus MeSH
- lymfoidní tkáň metabolismus MeSH
- mutace genetika MeSH
- proteiny Drosophily metabolismus MeSH
- tukové těleso metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Monocytes play an essential role in the defense against bacterial pathogens. Bone marrow (BM) and peripheral blood (PB) monocytes in pigs consist of the main "steady-state" subpopulations: CD14 hi/CD163-/SLA-DR- and CD14 low/CD163+/SLA-DR+. During inflammation, the subpopulation of "inflammatory" monocytes expressing very high levels of CD163, but lacking the SLA-DR molecule (being CD14 low/CD163+/SLA-DR-) appears in the BM and PB and replaces the CD14 low/CD163+/SLA-DR+ subpopulation. However, current knowledge of monocyte migration into inflamed tissues in pigs is limited. The aim of the present study was to evaluate the distribution of "inflammatory" CD14 low/CD163+/SLA-DR- monocytes during experimental inflammation induced by Actinobacillus pleuropneumoniae (APP) and a possible role for chemokines in attracting "inflammatory" CD14 low/CD163+/SLA-DR- monocytes into the tissues. Monocyte subpopulations were detected by flow cytometry. Chemokines and chemokine receptors were detected by RT-qPCR. The "steady-state" monocytes were found in the BM, PB, spleen and lungs of control pigs. After APP-infection, "inflammatory" monocytes replaced the "steady-state" subpopulation in BM, PB, spleen and moreover, they appeared in an unaffected area, demarcation zone and necrotic area of the lungs and in tracheobronchial lymph nodes. They did not appear in mesenteric lymph nodes. Levels of mRNA for various chemokines with their appropriate receptors were found to be elevated in BM (CCL3-CCR1/CCR5, CCL8-CCR2/CCR5, CCL19-CCR7), necrotic area of the lungs (CCL3-CCR1, CCL5-CCR1/CCR3, CCL11-CCR3, CCL22/CCR4) and tracheobronchial lymph nodes (CCL3-CCR1) and therefore they could play a role in attracting monocytes into inflamed tissues. In conclusion, "inflammatory" monocytes appear in different lymphoid tissues and the lungs after APP infection in pigs. Various chemokines could drive this process.
- MeSH
- Actinobacillus pleuropneumoniae fyziologie MeSH
- antigeny diferenciační myelomonocytární metabolismus MeSH
- CD antigeny metabolismus MeSH
- chemokiny genetika metabolismus MeSH
- infekce bakteriemi rodu Actinobacillus imunologie mikrobiologie veterinární MeSH
- lymfoidní tkáň metabolismus MeSH
- messenger RNA genetika MeSH
- monocyty cytologie metabolismus MeSH
- nemoci prasat imunologie mikrobiologie MeSH
- plíce metabolismus MeSH
- prasata MeSH
- průtoková cytometrie veterinární MeSH
- receptory buněčného povrchu metabolismus MeSH
- receptory chemokinů genetika metabolismus MeSH
- zánět mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Experimental and clinical studies have shown that autoimmunity-causing diabetes may be abrogated by immune intervention. Several anti-T-lymphocyte antibodies focus on distinct T-cell targets. We tested the effect of murine anti-thymocyte globulin (ATG; Genzyme, Framingham, MA) in peripheral lymphoid organs of non-obese diabetic (NOD) mice after the onset of hyperglycemia. METHODS: Diabetic NOD mice were treated with two doses of ATG (1 mg totally) or maintained without treatment as controls. Blood glucose levels were monitored twice a week. The mice were terminated at day 0, 7, 14, or 28 after the initiation of the study. Subpopulations of T-lymphocytes and FoxP3+ (forkhead box P3 positive) regulatory T-cells were analyzed among elements isolated from the spleen and pancreatic lymph nodes. RESULTS: Mice with blood glucose levels greater than 13 mmol/L were included in the study. Diabetes remission occurred in 16% (3/19) of mice treated with ATG. Only one case of remission was observed in the control group (6%; 1/16). ATG therapy a significantly decreased the CD8+/CD4+ T-lymphocyte ratio. Among splenocytes, a significant difference was detected only on day 7 (0.069 versus 0.198 T-lymphocyte ratio); in lymph nodes, a decrease was observed on day 28 (0.21 versus 0.51 T-lymphocytes ratio). The regulatory T-cells population increased after ATG administration compared with the control group at day 7 (16.2% versus 10.8% in CD4+ splenocytes; 20.7% versus 10.3% in CD4+ lymph node cells). However, the increased FoxP3+ cell population was not durable. CONCLUSIONS: ATG treatment of diabetic NOD mice showed an immunoregulatory effect in peripheral lymphoid tissue with a significantly deceased CD8+/CD4+ ratio, which, however, did not normalize the metabolic parameters in a short period after the onset of overt diabetes.
- MeSH
- antilymfocytární sérum terapeutické užití MeSH
- autoimunita MeSH
- časové faktory MeSH
- diabetes mellitus 1. typu imunologie terapie MeSH
- experimentální diabetes mellitus imunologie terapie MeSH
- glukózový toleranční test MeSH
- hyperglykemie imunologie MeSH
- imunitní systém MeSH
- krevní glukóza metabolismus MeSH
- lymfoidní tkáň metabolismus MeSH
- myši inbrední NOD MeSH
- myši MeSH
- průtoková cytometrie metody MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Due to the persisting threat of development of new highly pathogenic influenza A subtypes, a mucosal vaccination which would induce a potent and cross-protective reaction is desirable. We succeeded in mucosal immunization of mice with an inactivated influenza A virus by using delipidated Bacillus firmus (DBF) as adjuvant. The mechanism of adjuvant effect was followed in NALT by comparing the response after intranasal immunization by inactivated influenza virus type A (H1N1) alone, adjuvant alone (DBF), or by a mixture of virus+DBF. Expression of selected gene groups was tested via qPCR at 7 different time-points: cytokines (IL-2, IFN-γ, IL-4, IL-6, and IL-10), type I interferons (IFN-α4, IFN-α11, IFN-α12, and IFN-β), toll-like receptors (TLR2, TLR3, TLR7, and TLR9), iNOS and CCR7. Intranasally administered DBF and the mixture of virus+DBF induced an elevated expression of IFN-γ, IL-6 and IL-10 cytokines, type I interferons, iNOS, and pDC markers in NALT. Multimarker qPCR data was analyzed by relative quantification and by principal component analysis. DBF has been shown to be a very efficient adjuvant for the stimulation of innate immunity after IN immunization. DBF accelerated, increased, and prolonged the antiviral response.
- MeSH
- adjuvancia imunologická aplikace a dávkování MeSH
- analýza hlavních komponent MeSH
- aplikace intranazální MeSH
- Bacillus imunologie MeSH
- časové faktory MeSH
- cytokiny genetika MeSH
- exprese genu účinky léků MeSH
- imunizace metody MeSH
- interferon typ I genetika MeSH
- interleukin-10 genetika MeSH
- interleukin-2 genetika MeSH
- lymfoidní tkáň metabolismus MeSH
- membránové glykoproteiny genetika MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nazofarynx metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- synergismus léků MeSH
- toll-like receptor 2 genetika MeSH
- toll-like receptor 3 genetika MeSH
- toll-like receptor 7 genetika MeSH
- toll-like receptor 9 genetika MeSH
- toll-like receptory genetika MeSH
- vakcíny proti chřipce aplikace a dávkování imunologie MeSH
- virus chřipky A, podtyp H1N1 imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Celulitida je označení pro tzv. pomerančovou kůži. Projevuje se ztluštěním a zhruběním kůže a podkožního vaziva v oblasti hýždí, stehen, boků, břicha a paží. Článek podává přehled o etiologii, klasifikaci, klinickém obraze a komplexní péči.
Cellulite is a name for so-called orange peel syndrome. It manifests by thickening and roughening of the skin and subcutaneous connective tissue in the area of pelvis, hips, abdomen and upper limbs. This article summarizes etiology, classification, clinical picture and complex therapy.
- MeSH
- celulitida etiologie terapie MeSH
- lidé MeSH
- lymfoidní tkáň metabolismus patofyziologie MeSH
- masáž metody přístrojové vybavení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- fosfoproteiny genetika chemie metabolismus MeSH
- lidé MeSH
- lymfoidní tkáň metabolismus MeSH
- membránové proteiny genetika izolace a purifikace metabolismus MeSH
- receptory antigenů B-buněk metabolismus MeSH
- receptory Fc metabolismus MeSH
- transdukce genetická MeSH
- transportní proteiny genetika izolace a purifikace metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
