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.
- Keywords
- únikové strategie mikroorganismů,
- MeSH
- Host-Pathogen Interactions MeSH
- Humans MeSH
- Microbiological Phenomena * MeSH
- Immunity, Innate * MeSH
- Trained Immunity MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Antigen-presenting cells (APCs) are master regulators of the immune response by directly interacting with T cells to orchestrate distinct functional outcomes. Several types of professional APC exist, including conventional dendritic cells, B cells and macrophages, and numerous other cell types have non-classical roles in antigen presentation, such as thymic epithelial cells, endothelial cells and granulocytes. Accumulating evidence indicates the presence of a new family of APCs marked by the lineage-specifying transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and demonstrates that these APCs have key roles in shaping immunity, inflammation and tolerance, particularly in the context of host-microorganism interactions. These RORγt+ APCs include subsets of group 3 innate lymphoid cells, extrathymic autoimmune regulator-expressing cells and, potentially, other emerging populations. Here, we summarize the major findings that led to the discovery of these RORγt+ APCs and their associated functions. We discuss discordance in recent reports and identify gaps in our knowledge in this burgeoning field, which has tremendous potential to advance our understanding of fundamental immune concepts.
Protease inhibitors regulate various biological processes and prevent host tissue/organ damage. Specific inhibition/regulation of proteases is clinically valuable for treating several diseases. Psoriasis affects the skin in the limbs and scalp of the body, and the contribution of cysteine and serine proteases to the development of skin inflammation is well documented. Cysteine protease inhibitors from ticks have high specificity, selectivity, and affinity to their target proteases and are efficient immunomodulators. However, their potential therapeutic effect on psoriasis pathogenesis remains to be determined. Therefore, we tested four tick cystatins (Sialostatin L, Sialostatin L2, Iristatin, and Mialostatin) in the recently developed, innate immunity-dependent mannan-induced psoriasis model. We explored the effects of protease inhibitors on clinical symptoms and histological features. In addition, the number and percentage of immune cells (dendritic cells, neutrophils, macrophages, and γδT cells) by flow cytometry, immunofluorescence/immunohistochemistry and, the expression of pro-inflammatory cytokines (TNF-a, IL-6, IL-22, IL-23, and IL-17 family) by qPCR were analyzed using skin, spleen, and lymph node samples. Tick protease inhibitors have significantly decreased psoriasis symptoms and disease manifestations but had differential effects on inflammatory responses and immune cell populations, suggesting different modes of action of these inhibitors on psoriasis-like inflammation. Thus, our study demonstrates, for the first time, the usefulness of tick-derived protease inhibitors for treating skin inflammation in patients.
- MeSH
- Dermatitis * MeSH
- Endopeptidases MeSH
- Cysteine Proteinase Inhibitors MeSH
- Protease Inhibitors MeSH
- Humans MeSH
- Mannans MeSH
- Immunity, Innate MeSH
- Peptide Hydrolases MeSH
- Psoriasis * chemically induced drug therapy MeSH
- Inflammation drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Acanthocephalans are obligate endoparasites characterised by the presence of a proboscis with hooks, which are used to adhere and perforate the intestinal wall of their hosts. Individuals of Echinorhynchus salobrensis Machado Filho, 1948 have been reported parasitising the piranhas Serrasalmus maculatus Kner and Serrasalmus marginatus Valenciennes in the upper Paraná River floodplain. Serrasalmus marginatus is considered non-native at this site, and its establishment occurred after the closure of the Itaipu Hydroelectric, which flooded a natural geographic barrier that separated two ecoregions in the Paraná River. Since they are phylogenetically close and have similar biological and ecological characteristics competition for resources caused the non-native species to become dominant over the native one. Considering the specificity of species of Echinorhynchus Zoega, 1776 in serrasalmids, we evaluated the distribution of E. salobrensis along the gastrointestinal tract of S. maculatus and S. marginatus from the upper Paraná River floodplain. All parasites indices of E. salobrensis were higher in the invasive host S. marginatus when compared to the native S. maculatus. There were no significant interaction effects between host species and sex, and host species and/or sex in the presence of the parasite. When we evaluated the effect of E. salobrensis parasitism on the different gut regions and accessory organs, total abundance was significant in the stomach and caecum organs, and in the first and second regions of the intestine. None of the analytical approaches tested showed an effect of the sex of the host or the sex of the parasite on the presence and abundance of the parasite in the gastrointestinal tract. Studies on acanthocephalan parasitism in fish in Brazil focus on fish farm. The fact that two species of selvage carnivorous fish present high rates of acanthocephalan parasitism, added to the fact that most studies with this group are on farmed fish fed with feed, only emphasise the need for continuity in studies of acanthocephalans in the parasitology of aquatic organisms.
- MeSH
- Acanthocephala * MeSH
- Characiformes * MeSH
- Humans MeSH
- Parasites * MeSH
- Rivers MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Brazil MeSH
Tick-borne encephalitis (TBE) is a neuroviral disease that ranges in severity from a mild febrile illness to a severe and life-threatening meningoencephalitis or encephalomyelitis. There is increasing evidence that susceptibility to tick-borne encephalitis virus (TBEV)-induced disease and its severity are largely influenced by host genetic factors, in addition to other virus- and host-related factors. In this study, we investigated the contribution of selected single nucleotide polymorphisms (SNPs) in innate immunity genes to predisposition to TBE in humans. More specifically, we investigated a possible association between SNPs rs304478 and rs303212 in the gene Interferon Induced Protein With Tetratricopeptide Repeats 1 (IFIT1), rs7070001 and rs4934470 in the gene Interferon Induced Protein With Tetratricopeptide Repeats 2 (IFIT2), and RIG-I (Retinoic acid-inducible gene I) encoding gene DDX58 rs311795343, rs10813831, rs17217280 and rs3739674 SNPs with predisposition to TBE in population of the Czech Republic, where TBEV is highly endemic. Genotypic and allelic frequencies for these SNPs were analyzed in 247 nonimmunized TBE patients and compared with 204 control subjects. The analysis showed an association of IFIT1 rs304478 SNP and DDX58 rs3739674 and rs17217280 SNPs with predisposition to TBE in the Czech population indicating novel risk factors for clinical TBE but not for disease severity. These results also highlight the role of innate immunity genes in TBE pathogenesis.
- MeSH
- Genotype MeSH
- Interferons genetics MeSH
- Polymorphism, Single Nucleotide MeSH
- Encephalitis, Tick-Borne * genetics epidemiology MeSH
- Humans MeSH
- Immunity, Innate genetics MeSH
- Encephalitis Viruses, Tick-Borne * genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front line of host defence. Understanding the molecular mechanisms of innate immunity responses is an important prerequisite for the design of effective antivirotics. This review focuses on the present state of knowledge surrounding the mechanisms of viral DNA genome sensing and the main induced pathways of innate immunity responses. The studies that have been performed to date indicate that herpesviruses, adenoviruses, and polyomaviruses are sensed by various DNA sensors. In non-immune cells, STING pathways have been shown to be activated by cGAS, IFI16, DDX41, or DNA-PK. The activation of TLR9 has mainly been described in pDCs and in other immune cells. Importantly, studies on herpesviruses have unveiled novel participants (BRCA1, H2B, or DNA-PK) in the IFI16 sensing pathway. Polyomavirus studies have revealed that, in addition to viral DNA, micronuclei are released into the cytosol due to genotoxic stress. Papillomaviruses, HBV, and HIV have been shown to evade DNA sensing by sophisticated intracellular trafficking, unique cell tropism, and viral or cellular protein actions that prevent or block DNA sensing. Further research is required to fully understand the interplay between viruses and DNA sensors.
- MeSH
- DNA, Viral metabolism MeSH
- Herpesviridae * genetics metabolism MeSH
- DNA Virus Infections * MeSH
- Humans MeSH
- Polyomavirus * genetics MeSH
- Immunity, Innate MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
OBJECTIVES: To investigate the fitness effects of large blaCTX-M-15-harbouring F2:A1:B- plasmids on their native Escherichia coli ST131 H30Rx hosts. METHODS: We selected five E. coli ST131 H30Rx isolates of diverse origin, each carrying an F2:A1:B- plasmid with the blaCTX-M-15 gene. The plasmid was eliminated from each isolate by displacement using an incompatible curing plasmid, pMDP5_cureEC958. WGS was performed to obtain complete chromosome and plasmid sequences of original isolates and to detect chromosomal mutations in 'cured' clones. High-throughput competition assays were conducted to determine the relative fitness of cured clones compared with the corresponding original isolates. RESULTS: We were able to successfully eliminate the F2:A1:B- plasmids from all five original isolates using pMDP5_cureEC958. The F2:A1:B- plasmids produced non-significant fitness effects in three isolates and moderate reductions in relative fitness (3%-4%) in the two remaining isolates. CONCLUSIONS: We conclude that F2:A1:B- plasmids pose low fitness costs in their E. coli ST131 H30Rx hosts. This plasmid-host fitness compatibility is likely to promote the maintenance of antibiotic resistance in this clinically important E. coli lineage.
Aged people are the most susceptible group to COVID-19 infection. Immunosenescence characterized by impairment of immune function with inflamm-aging contributes to pathophysiological alterations, among which endocrine and metabolic diseases are not exception. Diabetes, obesity along with impairment of disorders of thyroid functions are the most frequent ones, the common feature of which is failure of immune system including autoimmune processes. In the minireview we discussed how COVID-19 and aging impact innate and adaptive immunity, diabetes and selected neuroendocrine processes. Mentioned is also beneficial effect of vitamin D for attenuation of these diseases and related epigenetic issues. Particular attention is devoted to the role of ACE2 protein in the light of its intimate link with renin-angiotensin regulating system.
- MeSH
- Adaptive Immunity MeSH
- COVID-19 immunology metabolism physiopathology virology MeSH
- Endocrine System immunology metabolism physiopathology virology MeSH
- Immunosenescence MeSH
- Host-Pathogen Interactions MeSH
- Humans MeSH
- Immunity, Innate MeSH
- Renin-Angiotensin System * MeSH
- SARS-CoV-2 immunology pathogenicity MeSH
- Aging immunology metabolism MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The 3'-5', 3'-5' cyclic dinucleotides (3'3'CDNs) are bacterial second messengers that can also bind to the stimulator of interferon genes (STING) adaptor protein in vertebrates and activate the host innate immunity. Here, we profiled the substrate specificity of four bacterial dinucleotide synthases from Vibrio cholerae (DncV), Bacillus thuringiensis (btDisA), Escherichia coli (dgcZ), and Thermotoga maritima (tDGC) using a library of 33 nucleoside-5'-triphosphate analogues and then employed these enzymes to synthesize 24 3'3'CDNs. The STING affinity of CDNs was evaluated in cell-based and biochemical assays, and their ability to induce cytokines was determined by employing human peripheral blood mononuclear cells. Interestingly, the prepared heterodimeric 3'3'CDNs bound to the STING much better than their homodimeric counterparts and showed similar or better potency than bacterial 3'3'CDNs. We also rationalized the experimental findings by in-depth STING-CDN structure-activity correlations by dissecting computed interaction free energies into a set of well-defined and intuitive terms. To this aim, we employed state-of-the-art methods of computational chemistry, such as quantum mechanics/molecular mechanics (QM/MM) calculations, and complemented the computed results with the {STING:3'3'c-di-ara-AMP} X-ray crystallographic structure. QM/MM identified three outliers (mostly homodimers) for which we have no clear explanation of their impaired binding with respect to their heterodimeric counterparts, whereas the R2 = 0.7 correlation between the computed ΔG'int_rel and experimental ΔTm's for the remaining ligands has been very encouraging.
- MeSH
- Bacillus thuringiensis enzymology ultrastructure MeSH
- Cytokines chemistry genetics MeSH
- Escherichia coli enzymology ultrastructure MeSH
- Crystallography, X-Ray MeSH
- Quantum Theory MeSH
- Leukocytes, Mononuclear chemistry enzymology MeSH
- Humans MeSH
- Membrane Proteins chemistry genetics ultrastructure MeSH
- Nucleotides biosynthesis chemistry genetics MeSH
- Immunity, Innate genetics MeSH
- Substrate Specificity MeSH
- Thermotoga maritima enzymology ultrastructure MeSH
- Vibrio cholerae enzymology ultrastructure MeSH
- Structure-Activity Relationship * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Neutrophils are innate immune cells with important roles in antimicrobial defense. However, impaired or dysregulated neutrophil function can result in host tissue damage, loss of homeostasis, hyperinflammation or pathological immunosuppression. A central link between neutrophil activation and immune outcomes is emerging to be the calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway, which is activated by neutrophil detection of a microbial threat via pattern recognition receptors and results in inflammatory cytokine production. This potent pro-inflammatory pathway is also the target of several immunosuppressive drugs used for the treatment of autoimmune disorders, during solid organ and hematopoietic cell transplantations, and as a part of anti-cancer therapy: but what effects these drugs have on neutrophil function, and their broader consequences for immune homeostasis and microbial defense are not yet known. Here, we bring together the emerging literature describing pathology- and drug- induced neutrophil impairment, with particular focus on their effects on calcineurin-NFAT signaling in the innate immune compartment.
- MeSH
- Cytokines immunology metabolism MeSH
- Homeostasis immunology MeSH
- Immune Tolerance immunology MeSH
- Calcineurin immunology metabolism MeSH
- Humans MeSH
- Inflammation Mediators immunology metabolism MeSH
- Neutrophils immunology metabolism MeSH
- Immunity, Innate immunology MeSH
- Receptors, Pattern Recognition immunology metabolism MeSH
- Signal Transduction immunology MeSH
- NFATC Transcription Factors immunology metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
