innate recognition
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Mikroorganismy si během evoluce vyvinuly širokou škálu strategií, jak uniknout vrozenému i adaptivnímu imunitnímu systému, a některým těmto strategiím se věnujeme v našem přehledu. Mikroorganismy mohou využívat podobnost svých proteinů s proteiny hostitele, produkovat protizánětlivé faktory, narušovat komplementový systém, ovlivňovat funkci a blokovat syntézu cytokinů, inhibovat rozpoznávání imunoglobulinů, snižovat expresi a modifikovat antigeny na svém povrchu, narušovat zpracování a prezentaci antigenu imunitními buňkami, vstupovat do imunitních buněk, ovlivňovat apoptózu buněk, modulovat funkce imunitních buněk nebo ovlivňovat produkci hormonů. S těmito únikovými strategiemi je nutné počítat při léčbě infekčních onemocnění.
Microorganisms have evolved a wide variety of strategies to evade both the innate and adaptive immune systems during evolution, and some of these strategies are addressed in our review. Microorganisms can use the similarity of their proteins to host proteins, produce anti-inflammatory factors, disrupt the complement system, affect the function and block the synthesis of cytokines, inhibit the recognition of immunoglobulins, reduce the expression and modify antigens on their surface, disrupt the processing and presentation of antigen by immune cells, enter immune cells , influence cell apoptosis, modulate immune cell functions or influence hormone production. These escape strategies must be taken into account when treating infectious diseases.
- Klíčová slova
- únikové strategie mikroorganismů,
- MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- mikrobiologické jevy * MeSH
- přirozená imunita * MeSH
- trénovaná imunita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to its profound implications for the health and well-being of the aging population. As people age, a multitude of alterations occur within the immune system, affecting both innate and adaptive immunity. In the realm of innate immunity, aging brings about changes in the number and function of various immune cells, including neutrophils, monocytes, and macrophages. Additionally, certain immune pathways, like the cGAS-STING, become activated. These alterations can potentially result in telomere damage, the disruption of cytokine signaling, and impaired recognition of pathogens. The adaptive immune system, too, undergoes a myriad of changes as age advances. These include shifts in the number, frequency, subtype, and function of T cells and B cells. Furthermore, the human gut microbiota undergoes dynamic changes as a part of the aging process. Notably, the interplay between immune changes and gut microbiota highlights the gut's role in modulating immune responses and maintaining immune homeostasis. The gut microbiota of centenarians exhibits characteristics akin to those found in young individuals, setting it apart from the microbiota observed in typical elderly individuals. This review delves into the current understanding of how aging impacts the immune system and suggests potential strategies for reversing aging through interventions in immune factors.
- MeSH
- adaptivní imunita * MeSH
- lidé MeSH
- přirozená imunita * MeSH
- stárnutí * imunologie MeSH
- střevní mikroflóra * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers. METHODS: We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria. RESULTS: qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo. DISCUSSION: Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.
- MeSH
- Aeromonas hydrophila * imunologie MeSH
- cytokiny * metabolismus imunologie MeSH
- erytrocyty * imunologie metabolismus MeSH
- fagocytóza imunologie MeSH
- gramnegativní bakteriální infekce * imunologie MeSH
- kapři * imunologie mikrobiologie MeSH
- nemoci ryb * imunologie mikrobiologie MeSH
- PAMP struktury imunologie MeSH
- přirozená imunita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
There is increasing knowledge in the recognition of individuals at risk for progression to rheumatoid arthritis (RA) before the clinical manifestation of the disease. This prodromal phase preceding the manifestation of RA may represent a "window of opportunity" for preventive interventions that may transform the clinical approach to this disease. However, limited evidence exists in support of effective interventions to delay the onset or even halt the manifestation of RA. Given the multifactorial nature of RA development and disease progression, the latest guidelines for established RA stress the use of integrative interventions and multidisciplinary care strategies, combining pharmacologic treatment with non-pharmacological approaches. Accordingly, individuals at risk of RA could be offered an integrative, multifactorial intervention approach. Current data point toward pharmacological intervention reverting the subclinical inflammation and delay in the disease onset. In addition, targeting life style modifiable factors (smoking cessation, dental health, physical activity, and diet) may presumably improve RA prognosis in individuals at risk, mainly by changes in epigenetics, autoantibodies, cytokines profiles, and microbiome. Nonetheless, the benefits of multidisciplinary interventions to halt the manifestation of RA in at-risk individuals remain unknown. As there is a growing knowledge of possible pharmacological intervention in the preclinical phase, this narrative review aims to provide a comprehensive overview of non-pharmacological treatments in individuals at risk of RA. Considering the mechanisms preceding the clinical manifestation of RA we explored all aspects that would be worth modifying and that would represent an integrative non-pharmacological care for individuals at risk of RA.
- MeSH
- autoprotilátky MeSH
- lidé MeSH
- prognóza MeSH
- revmatoidní artritida * terapie farmakoterapie MeSH
- zánět MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: E. coli O83 (Colinfant Newborn) is a Gram-negative (G-) probiotic bacterium used in the clinic. When administered orally, it reduces allergic sensitisation but not allergic asthma. Intranasal administration offers a non-invasive and convenient delivery method. This route bypasses the gastrointestinal tract and provides direct access to the airways, which are the target of asthma prevention. G- bacteria such as E. coli O83 release outer membrane vesicles (OMVs) to communicate with the environment. Here we investigate whether intranasally administered E. coli O83 OMVs (EcO83-OMVs) can reduce allergic airway inflammation in mice. METHODS: EcO83-OMVs were isolated by ultracentrifugation and characterised their number, morphology (shape and size), composition (proteins and lipopolysaccharide; LPS), recognition by innate receptors (using transfected HEK293 cells) and immunomodulatory potential (in naïve splenocytes and bone marrow-derived dendritic cells; BMDCs). Their allergy-preventive effect was investigated in a mouse model of ovalbumin-induced allergic airway inflammation. RESULTS: EcO83-OMVs are spherical nanoparticles with a size of about 110 nm. They contain LPS and protein cargo. We identified a total of 1120 proteins, 136 of which were enriched in OMVs compared to parent bacteria. Proteins from the flagellum dominated. OMVs activated the pattern recognition receptors TLR2/4/5 as well as NOD1 and NOD2. EcO83-OMVs induced the production of pro- and anti-inflammatory cytokines in splenocytes and BMDCs. Intranasal administration of EcO83-OMVs inhibited airway hyperresponsiveness, and decreased airway eosinophilia, Th2 cytokine production and mucus secretion. CONCLUSIONS: We demonstrate for the first time that intranasally administered OMVs from probiotic G- bacteria have an anti-allergic effect. Our study highlights the advantages of OMVs as a safe platform for the prophylactic treatment of allergy. Video Abstract.
- MeSH
- alergie * prevence a kontrola metabolismus MeSH
- bronchiální astma * metabolismus MeSH
- Escherichia coli MeSH
- extracelulární vezikuly * metabolismus MeSH
- HEK293 buňky MeSH
- lidé MeSH
- lipopolysacharidy MeSH
- myši MeSH
- přirozená imunita MeSH
- probiotika * farmakologie MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) and candidalysin. Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. Saps also hydrolyze amyloid precursor protein (APP) into amyloid β (Aβ)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while candidalysin engages the integrin CD11b (Mac-1) on microglia. Recognition of Aβ-like peptides and candidalysin promotes fungal clearance from the brain, and disruption of candidalysin recognition through CD11b markedly prolongs C. albicans cerebral mycosis. Thus, C. albicans is cleared from the brain through innate immune mechanisms involving Saps, Aβ, candidalysin, and CD11b.
- MeSH
- Alzheimerova nemoc metabolismus mikrobiologie MeSH
- amyloidní beta-protein metabolismus MeSH
- antigeny CD11b * metabolismus MeSH
- Candida albicans metabolismus MeSH
- fungální proteiny metabolismus MeSH
- mikroglie * metabolismus mikrobiologie MeSH
- mykózy * genetika metabolismus MeSH
- myši MeSH
- toll-like receptor 4 * metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Organoid cultures may express several types of pattern-recognition receptors and in particular toll-like receptors, representing an extremely efficient and innovative system to understand how pathogen-associated molecular patterns exposure may affect the immunity, the growth, or differentiation of complex tissues. Here, we describe how to generate lung organoids from human-induced pluripotent stem cells. Three-dimensional (3D) cultures are then stimulated with different toll-like receptor ligands derived from fungi or with Aspergillus fumigatus. RNA sequencing may be performed upon organoid cultures to understand host-pathogen innate immune interactions.
- MeSH
- Aspergillus fumigatus * MeSH
- buněčná diferenciace MeSH
- houby * MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- organoidy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Xenobiotic receptors, such as the pregnane X receptor, regulate multiple host physiologic pathways including xenobiotic metabolism, certain aspects of cellular metabolism, and innate immunity. These ligand-dependent nuclear factors regulate gene expression via genomic recognition of specific promoters and transcriptional activation of the gene. Natural or endogenous ligands are not commonly associated with this class of receptors; however, since these receptors are expressed in a cell-type specific manner in the liver and intestines, there has been significant recent effort to characterize microbially derived metabolites as ligands for these receptors. In general, these metabolites are thought to be weak micromolar affinity ligands. This journal anniversary minireview focuses on recent efforts to derive potentially nontoxic microbial metabolite chemical mimics that could one day be developed as drugs combating xenobiotic receptor-modifying pathophysiology. The review will include our perspective on the field and recommend certain directions for future research. SIGNIFICANCE STATEMENT: Xenobiotic receptors (XRs) regulate host drug metabolism, cellular metabolism, and immunity. Their presence in host intestines allows them to function not only as xenosensors but also as a response to the complex metabolic environment present in the intestines. Specifically, this review focuses on describing microbial metabolite-XR interactions and the translation of these findings toward discovery of novel chemical mimics as potential drugs of the future for diseases such as inflammatory bowel disease.
Sepse představuje heterogenní dynamický syndrom, jehož podstatou je závažná orgánová dysfunkce způsobená dysregulovanou odpovědí hostitele na infekci. Klíčovou úlohu v reakci na infekční inzult hraje patofyziologie imunitního systému, jak vrozená, tak získaná imunitní odpověď při rozvoji sepse či septického šoku, který představuje nejtěžší formu této nozologické jednotky. Nekontrolovaná a pozdě diagnostikovaná infekce může fatálně ovlivnit i doposud zdravé jedince, zvýšeně náchylní jsou chroničtí pacienti s komorbiditami. Dramaticky nejvíce ohroženou skupinu představují kriticky nemocní pacienti všech věkových skupin se selháváním základních životních funkcí na jednotkách intenzivní péče. Rychlá a efektivní diagnostika hrozícího rozvoje septického stavu je pro zvládnutí nemoci a dobrý klinický výsledek rozhodující. Současná medicína využívá celou řadu diagnostických možností od stále důležité a neopomenutelné pečlivé anamnézy až po nejsložitější laboratorní, funkční či zobrazovací metody. Výraznou pomoc při časném rozpoznání sepse představují biomarkery, které by ideálně měly být komplexní pro časnou diagnostiku, prognózu, stratifikaci rizika onemocnění a jeho léčbu. Autoři v prezentaci předkládají výsledky studií zaměřené na dva parametry, které jsou levné, rychle dostupné a jsou součástí rutinně indikovaného vyšetření krevního obrazu s diferenciálním rozpočtem krevních buněk. Frakce nezralých trombocytů a granulocytů jsou předmětem zájmu klinických i výzkumných pracovníků při předpovědi zánětlivého procesu i v predikci tíže onemocnění a mortality. Následující text shrnuje dosavadní poznatky o nezralých formách krevních destiček a nezralých granulocytech v problematice sepse u pacientů v prostředí intenzivní péče.
Sepsis is a heterogeneous dynamic syndrome characterized by severe organ dysfunction caused by a dysregulated host response to infection. The innate and adaptive immune response plays a key role in the response to infectious insult in the development of sepsis or septic shock, the most severe form of this nosological entity. Uncontrolled and late diagnosed infection can be fatal even in previously healthy individuals, chronic patients with comorbidities have an increased risk of developing sepsis. Critically ill patients of all ages with failure of basic life functions in intensive care units are the most at risk group. Rapid and effective diagnosis of impending septicemia is crucial for disease management and good clinical outcome. Modern medicine uses a range of diagnostic options from the ever-important and unforgettable anamnesis taking to the most sophisticated laboratory, functional or imaging methods. Biomarkers play an important aid in the early recognition of sepsis and should ideally be comprehensive for early diagnosis, prognosis, disease risk stratification and treatment. This review article notes two parameters that are inexpensive, rapidly available, and part of the routinely indicated blood count with differential blood cell budget. Immature platelet and granulocyte fractions are of interest to clinicians and researchers in the diagnosis of sepsis and in the prediction of disease severity and mortality. The following text summarizes the current knowledge about immature platelet and immature granulocyte forms, mainly in the field of sepsis in intensive care patients.
- MeSH
- časná diagnóza * MeSH
- granulocyty fyziologie patologie MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- sepse * diagnóza patofyziologie prevence a kontrola MeSH
- trombocytopenie diagnóza krev patologie MeSH
- trombocyty fyziologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
