Bakteriální lyzáty nespecificky stimulují celkovou imunitu organismu. Působí na nespecifické obranné mechanismy, což vede ke zvýšení IgA na sliznicích, fagocytární aktivitě a produkci interferonu gama. Mohou také stimulovat tvorbu specifických protilátek proti bakteriálním antigenům, které tvoří přípravek. V mnoha klinických studiích bylo prokázáno, že perorální bakteriální lyzáty snižují četnost opakovaných respiračních infekcí u dětí i dospělých a snižují potřebu podávání antibiotik.

Bacterial lysates stimulate the general immunity of the body in a non-specific way. They act on non-specific defense mechanisms, leading to an increase IgA in mucous membranes, phagocytic activity and interferon gamma production. They can also stimulate the production of specific antibodies against the bacterial antigens that make up the preparation. In many clinical trials, oral bacterial lysates have been shown to decrease the risk of recurrent respiratory infections in children and adults and reduce the need for antibiotics.

• Klíčová slova
• bakteriální lyzáty,
• MeSH
• adaptivní imunita účinky léků   MeSH
• adjuvancia imunologická * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• infekce dýchací soustavy imunologie   patologie   prevence a kontrola   MeSH
• infekce močového ústrojí imunologie   prevence a kontrola   MeSH
• infekce reprodukčního traktu imunologie   MeSH
• lidé MeSH
• přirozená imunita účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Pilotní monocentrická studie vyhodnotila účinek přípravku Imunor na prevenci vzniku onemocnění covid-19 u 51 zdravotních sester ve Fakultní nemocnici Ostrava v období třetí vlny pandemie covidu-19 (varianta delta) v České republice. Primárním cílem studie bylo zjistit, zda pravidelné podávání přípravku Imunor po dobu 1 měsíce, po dobu 2 měsíců a v období 1 měsíc po ukončení podávání přípravku zabrání vzniku infekce SARS-CoV-2 u zdravotních sester pracujících v ambulantních a lůžkových provozech nemocnice v rizikovém prostředí možného kontaktu s pacienty s onemocněním covid-19. Sekundárním cílem studie bylo vyhodnotit, zda při onemocnění covidem-19 bude průběh onemocnění mírnější. Rovněž byla sledována potřeba hospitalizace studijních subjektů pro covid-19 a celková snášenlivost studijního přípravku. Jako kontrolní soubor byl použit soubor ostatních zdravotních sester pracujících ve stejné nemocnici, u kterých bylo v průběhu studie zahájeno očkování proti SARS-CoV-2.

A pilot monocentric study evaluated the effect of Imunor on the prevention of COVID-19 in 51 nurses at the University Hospital Ostrava during the third wave of the COVID-19 pandemic (delta variant) in the Czech Republic. The primary objective of the study was to determine whether regular administration of Imunor for 1 month, 2 months, and 1 month after discontinuation prevented SARS-CoV2 infection in nurses working in outpatient and inpatient settings in high-risk environments. with patients with COVID-19. The secondary objective of the study was to evaluate whether the course of the disease would be milder in COVID-19. The need for hospitalization of study subjects for COVID-19 and the overall tolerability of the study preparation were also monitored. A set of other nurses working at the same hospital who were vaccinated against SARS-Cov2 during the study was used as a control. Throughout the study period (during treatment and 1 month after treatment), only 2 nurses experienced a mild course of COVID-19 disease that did not require hospitalization, patients were only isolated for 2 weeks at home with only symptomatic treatment. and after 2 weeks they returned to full workload. Statistical analysis confirmed a statistically highly significant preventive effect (p ≤ 0.00001) for 70% of the study days. In the remaining 30% of days (when there was always only 1 nurse on incapacity for work), it was not possible to express statistical significance for a small number of study subjects.

• Klíčová slova
• Imunor,
• MeSH
• COVID-19 * prevence a kontrola   MeSH
• lidé MeSH
• pilotní projekty MeSH
• přirozená imunita účinky léků   MeSH
• transfer faktor * aplikace a dávkování   terapeutické užití   MeSH
• vakcíny proti COVID-19 MeSH
• zdravotní sestry MeSH
• Check Tag
• lidé MeSH

The role of immune system in carcinogenesis represents fundamental events associated with cancer eradication; however, tumor evolution is connected with various mechanisms of tumor evasion and progression of cancer. Based on recent evidence, phytochemicals are directly associated with immunomodulation of the innate and adaptive immunity via different mechanisms of action including stimulation and amplification of immune cells, humoral compartments, and associated molecules. This comprehensive study focuses on immunomodulating potential of phytochemicals (mixture in plants or separately such as individual phytochemical) and their impact on regulation of immune response during cancer development, immune tolerance, and immune escape. Clinical application of phytochemicals as modulators of host immunity against cancer may represent perspective approach in anticancer therapy.

• MeSH
• fytonutrienty terapeutické užití   MeSH
• imunologická tolerance účinky léků   MeSH
• imunomodulace účinky léků   MeSH
• karcinogeneze účinky léků   MeSH
• lidé MeSH
• nádory farmakoterapie   patologie   MeSH
• přirozená imunita účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Titanium dioxide nanoparticles (TiO2NPs) are revolutionizing biomedicine due to their potential application as diagnostic and therapeutic agents. However, the TiO2NP immune-compatibility remains an open issue, even for ethical reasons. In this work, we investigated the immunomodulatory effects of TiO2NPs in an emergent proxy to human non-mammalian model for in vitro basic and translational immunology: the sea urchin Paracentrotus lividus. To highlight on the new insights into the evolutionarily conserved intracellular signaling and metabolism pathways involved in immune-TiO2NP recognition/interaction we applied a wide-ranging approach, including electron microscopy, biochemistry, transcriptomics and metabolomics. Findings highlight that TiO2NPs interact with immune cells suppressing the expression of genes encoding for proteins involved in immune response and apoptosis (e.g. NF-κB, FGFR2, JUN, MAPK14, FAS, VEGFR, Casp8), and boosting the immune cell antioxidant metabolic activity (e.g. pentose phosphate, cysteine-methionine, glycine-serine metabolism pathways). TiO2NP uptake was circumscribed to phagosomes/phagolysosomes, depicting harmless vesicular internalization. Our findings underlined that under TiO2NP-exposure sea urchin innate immune system is able to control inflammatory signaling, excite antioxidant metabolic activity and acquire immunological tolerance, providing a new level of understanding of the TiO2NP immune-compatibility that could be useful for the development in Nano medicines.

• MeSH
• antioxidancia metabolismus   MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• fagocytóza účinky léků   MeSH
• genetická transkripce účinky léků   MeSH
• kultivované buňky MeSH
• nanočástice toxicita   MeSH
• Paracentrotus cytologie   účinky léků   imunologie   metabolismus   MeSH
• přirozená imunita účinky léků   genetika   MeSH
• titan toxicita   MeSH
• viabilita buněk účinky léků   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Circulating inflammatory monocytes are attracted to infected mucosa and differentiate into macrophage or dendritic cells endowed with enhanced bactericidal and antigen presenting capacities. In this brief Perspective we discuss the newly emerging insight into how the cAMP signaling capacity of Bordetella pertussis adenylate cyclase toxin manipulates the differentiation of monocytes and trigger dedifferentiation of the alveolar macrophages to facilitate bacterial colonization of human airways.

• MeSH
• adenylátcyklasový toxin farmakologie   fyziologie   MeSH
• alveolární makrofágy cytologie   účinky léků   MeSH
• AMP cyklický fyziologie   MeSH
• biologické modely MeSH
• Bordetella pertussis fyziologie   MeSH
• buněčná diferenciace MeSH
• dediferenciace buněk účinky léků   MeSH
• dýchací soustava účinky léků   imunologie   mikrobiologie   MeSH
• fagocytóza MeSH
• interakce hostitele a patogenu imunologie   MeSH
• lidé MeSH
• monocyty cytologie   účinky léků   MeSH
• myši MeSH
• prezentace antigenu účinky léků   MeSH
• přirozená imunita účinky léků   MeSH
• slizniční imunita účinky léků   MeSH
• systémy druhého messengeru účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Recombinant interferon-α (IFN-α) treatment functionally cures chronic hepatitis B virus (HBV) infection in some individuals and suppresses virus replication in hepatocytes infected in vitro. We studied the antiviral effect of conditioned media (CM) from peripheral blood mononuclear cells (PBMCs) stimulated with agonists of Toll-like receptors (TLRs) 2, 7, 8 and 9. We found that CM from PBMCs stimulated with dual-acting TLR7/8 (R848) and TLR2/7 (CL413) agonists were more potent drivers of inhibition of HBe and HBs antigen secretion from HBV-infected primary human hepatocytes (PHH) than CM from PBMCs stimulated with single-acting TLR7 (CL264) or TLR9 (CpG-B) agonists. Inhibition of HBV in PHH did not correlate with the quantity of PBMC-produced IFN-α, but it was a complex function of multiple secreted cytokines. More importantly, we found that the CM that efficiently inhibited HBV production in freshly isolated PHH via various cytokine repertoires and mechanisms did not reduce covalently closed circular (ccc)DNA levels. We confirmed our data with a cell culture model based on HepG2-NTCP cells and the plasmacytoid dendritic cell line GEN2.2. Collectively, our data show the importance of dual-acting TLR agonists inducing broad cytokine repertoires. The development of poly-specific TLR agonists provides novel opportunities towards functional HBV cure.

• MeSH
• buňky Hep G2 MeSH
• chronická hepatitida B virologie   MeSH
• cytokiny metabolismus   MeSH
• hepatocyty virologie   MeSH
• interferon alfa metabolismus   MeSH
• kruhová DNA metabolismus   MeSH
• kultivační média speciální farmakologie   MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé MeSH
• přirozená imunita účinky léků   MeSH
• replikace viru účinky léků   MeSH
• systémy cílené aplikace léků MeSH
• toll-like receptory agonisté   metabolismus   MeSH
• virus hepatitidy B fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We find that cardiac group 2 innate lymphoid cells (ILC2s) are essential for the development of IL-33-induced eosinophilic pericarditis. We show a pathogenic role for ILC2s in cardiac inflammation, in which ILC2s activated by IL-33 drive the development of eosinophilic pericarditis in collaboration with cardiac fibroblasts. ILCs, not T and B cells, are required for the development of pericarditis. ILC2s transferred to the heart of Rag2-/-Il2rg-/- mice restore their susceptibility to eosinophil infiltration. Moreover, ILC2s direct cardiac fibroblasts to produce eotaxin-1. We also find that eosinophils reside in the mediastinal cavity and that eosinophils transferred to the mediastinal cavity of eosinophil-deficient ΔdblGATA1 mice following IL-33 treatment migrate to the heart. Thus, the serous cavities may serve as a reservoir of cardiac-infiltrating eosinophils. In humans, patients with pericarditis show higher amounts of ILCs in pericardial fluid than do healthy controls and patients with other cardiac diseases. We demonstrate that ILCs play a critical role in pericarditis.

• MeSH
• chemokin CCL11 genetika   metabolismus   MeSH
• eozinofily účinky léků   patologie   MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• funkční vyšetření srdce účinky léků   MeSH
• interleukin 33 farmakologie   MeSH
• interleukin-1 receptor-like 1 protein nedostatek   metabolismus   MeSH
• interleukin-5 metabolismus   MeSH
• lidé MeSH
• lymfocyty účinky léků   imunologie   MeSH
• mediastinum patologie   MeSH
• myši inbrední BALB C MeSH
• náchylnost k nemoci MeSH
• perikarditida genetika   imunologie   patofyziologie   MeSH
• pohyb buněk účinky léků   MeSH
• přirozená imunita * účinky léků   MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• srdce účinky léků   patofyziologie   MeSH
• upregulace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Among the benzotriazole ultraviolet stabilizers (BUVSs), UV-234 and UV-320 are frequently detected in aquatic ecosystem. Despite the fact that these chemicals are present in low ng/L levels in surface water, they show high bio-accumulation potential and pose exposure risks to aquatic organisms. However, there are limited toxicological data available in fish. In this study, zebrafish embryos were exposed to 0.01, 0.1 and 1 μM UV-234 or UV-320 for up to 6 days. Developmental toxicity as well as effects on mitochondrial bioenergetics, immune system responses, and locomotor activity in zebrafish were measured. After UV-234 treatment (0.1-1 μM), hatching time of embryos was increased compared to controls. There was also a ∼20-40% reduction in non-mitochondrial respiration and oligomycin-dependent mitochondrial respiration in embryos treated with 1 μM UV-234 for 24 and 48 h respectively; conversely basal respiration and non-mitochondrial respiration were increased ∼20-30% in embryos treated with 1 μM UV-320 at 48 h. Transcript levels of sod1 were down-regulated with BUVSs while sod2 mRNA was highly up-regulated with both UV-234 and UV-320, suggesting an oxidative damage response. Considering that mitochondrial signaling regulates innate immune pathways, we measured the expression of immune related transcripts (tlr5a, tlr5b, mmp9, il8, tnfa, cxcl-C1c, nfkb1, and ifng). Of these, only il8 and cxcl-C1c mRNA were decreased in response to 0.1 μM UV-320. To associate early molecular events with behavior, locomotor activity was assessed. UV-234 reduced larval activity in a dark photokinesis assay by ∼15%, however behavioral responses at environmentally-relevant concentrations of BUVSs were not consistent across experiments nor BUVSs. These data suggest that BUVSs can perturb mitochondrial bioenergetics, embryonic development, and locomotor activity of zebrafish, but these responses appear to be dose-, time- and BUVSs dependent, suggesting these chemicals may have unique modes of action.

• MeSH
• dánio pruhované embryologie   metabolismus   MeSH
• embryonální vývoj účinky léků   MeSH
• energetický metabolismus fyziologie   MeSH
• larva účinky léků   MeSH
• lokomoce fyziologie   MeSH
• mitochondrie metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• přirozená imunita účinky léků   MeSH
• triazoly farmakologie   MeSH
• ultrafialové záření MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Plant phospholipase Ds (PLDs), essential regulators of phospholipid signaling, function in multiple signal transduction cascades; however, the mechanisms regulating PLDs in response to pathogens remain unclear. Here, we found that Arabidopsis (Arabidopsis thaliana) PLDδ accumulated in cells at the entry sites of the barley powdery mildew fungus, Blumeria graminis f. sp hordei Using fluorescence recovery after photobleaching and single-molecule analysis, we observed higher PLDδ density in the plasma membrane after chitin treatment; PLDδ also underwent rapid exocytosis. Fluorescence resonance energy transfer with fluorescence lifetime imaging microscopy showed that the interaction between PLDδ and the microdomain marker AtREMORIN1.3 (AtREM1.3) increased in response to chitin, indicating that exocytosis facilitates rapid, efficient sorting of PLDδ into microdomains upon pathogen stimulus. We further unveiled a trade-off between brefeldin A (BFA)-resistant and -sensitive pathways in secretion of PLDδ under diverse conditions. Upon pathogen attack, PLDδ secretion involved syntaxin-associated VAMP721/722-mediated exocytosis sensitive to BFA. Analysis of phosphatidic acid (PA), hydrogen peroxide, and jasmonic acid (JA) levels and expression of related genes indicated that the relocalization of PLDδ is crucial for its activation to produce PA and initiate reactive oxygen species and JA signaling pathways. Together, our findings revealed that the translocation of PLDδ to papillae is modulated by exocytosis, thus triggering PA-mediated signaling in plant innate immunity.plantcell;31/12/3015/FX1F1fx1.

• MeSH
• Arabidopsis genetika   imunologie   metabolismus   mikrobiologie   MeSH
• Ascomycota patogenita   MeSH
• brefeldin A imunologie   metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• chitin imunologie   metabolismus   MeSH
• cyklopentany metabolismus   MeSH
• exocytóza účinky léků   imunologie   MeSH
• fosfolipasa D genetika   metabolismus   MeSH
• kyseliny fosfatidové metabolismus   MeSH
• nemoci rostlin imunologie   mikrobiologie   MeSH
• oxylipiny metabolismus   MeSH
• peroxid vodíku metabolismus   MeSH
• přirozená imunita * účinky léků   MeSH
• proteiny huseníčku metabolismus   MeSH
• proteiny Qa-SNARE metabolismus   MeSH
• proteiny R-SNARE metabolismus   MeSH
• proteiny SNARE genetika   metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• signální transdukce imunologie   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The inhalation or application of nanoparticles (NPs) has serious impacts on immunological reactivity. However, the effects of NPs on the immune system are influenced by numerous factors, which cause a high variability in the results. Here, mice were exposed to a three month continuous inhalation of copper oxide (CuO) NPs, and at different time intervals (3, 14, 42 and 93 days), the composition of cell populations of innate and adaptive immunity was evaluated in the spleen by flow cytometry. The ability of spleen cells from exposed and control mice to respond to stimulation with T- or B-cell mitogens by proliferation and by production of cytokines IL-2, IL-6, IL-10, IL-17 and IFN-γ was characterized. The results showed that the inhalation of CuO NPs predominantly affects the cells of innate immunity (changes in the proportion of eosinophils, neutrophils, macrophages and antigen-presenting cells) with a minimal effect on the percentage of T and B lymphocytes. However, the proliferative and secretory activity of T cells was already significantly enhanced after 3 days from the start of inhalation, decreased on day 14 and normalized at the later time intervals. There was no correlation between the impacts of NPs on the cells of innate and adaptive immunity. The results have shown that the inhalation of CuO NPs significantly alters the composition of cell populations of innate immunity and modulates the proliferation and production of cytokines by cells of the adaptive immune system. However, the immunomodulatory effects of inhaled NPs strongly depend on the time of inhalation.

• MeSH
• adaptivní imunita účinky léků   MeSH
• aplikace inhalační MeSH
• cytokiny biosyntéza   MeSH
• kinetika MeSH
• měď aplikace a dávkování   toxicita   MeSH
• modely u zvířat MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nanočástice toxicita   MeSH
• přirozená imunita účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH