Germ-free model
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- MeSH
- gnotobiologické modely MeSH
- modely nemocí na zvířatech imunologie mikrobiologie MeSH
- novorozená zvířata imunologie MeSH
- prasata imunologie MeSH
- salmonelóza imunologie MeSH
- skot MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome's importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument.
- MeSH
- Bacteria MeSH
- gnotobiologické modely * MeSH
- karcinogeneze MeSH
- mikrobiota * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Bacteria that are highly virulent, expressing high infectivity, and able to survive nebulization, pose great risk to the human population. One of these is Francisella tularensis, the etiological agent of tularemia. F. tularensis is a subject of intense scientific interest due to the fact that vaccines for its immunoprophylaxis in humans are not yet routinely available. One of the substantial obstacles in developing such vaccines is our insufficient knowledge of processes that initiate and regulate the expression of effective protective immunity against intracellular bacteria. Here, we present data documenting the different pattern of cellular behavior occurring in an environment unaffected by microbiota using the model of germ-free mice mono-associated with F. tularensis subsp. holarctica strain LVS in comparison with a classic specific-pathogen-free murine model during early stages of infection.
- MeSH
- bakteriální vakcíny imunologie MeSH
- cytokiny metabolismus MeSH
- Francisella tularensis imunologie patogenita MeSH
- gnotobiologické modely imunologie MeSH
- interakce hostitele a patogenu imunologie MeSH
- mikrobiota MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- organismy bez specifických patogenů imunologie MeSH
- peritoneum mikrobiologie patologie MeSH
- přirozená imunita MeSH
- slezina mikrobiologie patologie MeSH
- tularemie imunologie mikrobiologie patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The mammalian microbiota plays a crucial role in the pathogenesis of many diseases. Thanks to recent advances in metagenomics, proteomics, and metabolomics, microbiome composition and metabolic activity can now be studied in detail. Results obtained by such fascinating and provocative studies would be meaningless without considering the perspective of the whole organism. Our work using gnotobiology as the major tool to unravel the mechanisms of host-microbe interaction has demonstrated the crucial role of microbiota in the initiation and progression of inflammation-associated colorectal neoplasia. Carcinogenesis in the gut is driven by the presence of potentially harmful microbes or by lack of protective ones, by the production of carcinogens generated by microbes, and by the induction of inflammation and modulation of the immune system. Here, we review these mechanisms with special emphasis on those where gnotobiology has yielded important insights.
- MeSH
- gnotobiologické modely * MeSH
- kolorektální nádory mikrobiologie MeSH
- lidé MeSH
- mikrobiota * MeSH
- modely nemocí na zvířatech * MeSH
- nádorové mikroprostředí MeSH
- zánět mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Metagenomic approaches are currently being used to decipher the genome of the microbiota (microbiome), and, in parallel, functional studies are being performed to analyze the effects of the microbiota on the host. Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization. Animals used as models of human diseases can be maintained in sterile conditions (isolators used for germ-free rearing) and specifically colonized with defined microbes (including non-cultivable commensal bacteria). The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models. Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia (i.e., using models of human inflammatory bowel disease and colorectal carcinoma). In contrast, a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Interestingly, the development of atherosclerosis in germ-free apolipoprotein E (ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals. Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota. Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial, disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components (e.g., probiotics and prebiotics) whose administration may aid in disease prevention and treatment.
- MeSH
- autoimunitní nemoci etiologie mikrobiologie MeSH
- gastrointestinální trakt mikrobiologie MeSH
- gnotobiologické modely MeSH
- imunita MeSH
- lidé MeSH
- metagenom imunologie MeSH
- modely nemocí na zvířatech MeSH
- nádory etiologie mikrobiologie MeSH
- sliznice imunologie MeSH
- zánět etiologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Germ-free animals (GF) are those without a microbiome since birth. This particular biological model has become one of special interest with the growing evidence of importance of the microbiome in the life, development, adaptation, and immunity of humans and animals in the environments in which they live. Anatomical differences observed in GF compared with conventionally-reared animals (CV) has given rise to the question of the influence of commensal microflora on the development of structure and function (even immunological) of the bowel. Only recently, thanks to achievements in microscopy and associated methods, structural differences can be better evaluated and put in perspective with the immunological characteristics of GF vs. CV animals. This study, using a GF rat model, describes for the first time the possible influence that the presence of commensal microflora, continuously stimulating mucosal immunity, has on the collagen scaffold organization of the colon mucosa. Significant differences were found between CV and GF mucosa structure with higher complexity in the CV rats associated to a more activated immune environment. The immunological data suggest that, in response to the presence of a microbiome, an effective homeostatic regulation in developed by the CV rats in healthy conditions to avoid inflammation and maintain cytokine levels near the spontaneous production found in the GF animals. The results indicated that collagen scaffold adapted to the immune microenvironment; therefore, it is apparent that the microbiome was able to condition the structure of the colon mucosa.
Germ-free animals have been used to define the vital role of commensal bacteria on the maturation of the host immune system. However, the role of bacterial residues in diet in this setting is poorly understood. Here we investigated the effect of bacterial contamination in sterile diet on the level of allergic sensitization in germ-free mice. Sterile grain-based diets ST1 and R03 were tested for the level of bacterial contamination. ST1 contained higher amount of bacterial DNA, approximately ten times more endotoxin, and induced higher, TLR4-dependent, cytokine production in dendritic cells compared to R03. In a germ-free mouse model of sensitization to the major birch pollen allergen Bet v 1, feeding on ST1 for at least two generations was associated with decreased production of allergen-specific IgE and IgG1 antibodies in sera in comparison to R03. Furthermore, reduced levels of allergen-specific and ConA-induced cytokines IL-4, IL-5 and IL-13 accompanied by increased levels of IFN-γ were detected in splenocytes cultures of these mice. Our results show that contamination of experimental diet with bacterial residues, such as endotoxin, significantly affects the development of allergic sensitization in germ-free mice. Therefore, careful selection of sterile food is critical for the outcomes of germ-free or gnotobiotic experimental models of immune-deviated diseases.
- MeSH
- alergie imunologie patologie MeSH
- antigeny rostlinné imunologie MeSH
- buněčná diferenciace účinky léků MeSH
- chov MeSH
- cytokiny biosyntéza MeSH
- dendritické buňky účinky léků MeSH
- dieta * MeSH
- DNA bakterií analýza MeSH
- endotoxiny toxicita MeSH
- epitopy imunologie MeSH
- gnotobiologické modely MeSH
- HEK293 buňky MeSH
- imunizace * MeSH
- imunoglobulin A imunologie MeSH
- imunoglobulin G imunologie MeSH
- kontaminace DNA MeSH
- kultivované buňky MeSH
- lidé MeSH
- ligandy MeSH
- mitogeny farmakologie MeSH
- myši inbrední BALB C MeSH
- slezina patologie MeSH
- toll-like receptor 4 metabolismus MeSH
- trávicí systém imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- B-lymfocyty fyziologie MeSH
- gnotobiologické modely imunologie MeSH
- imunizace MeSH
- plod imunologie MeSH
- prasata imunologie MeSH
- skot MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
Mucosal surfaces are colonized by highly diverse commensal microbiota. Coating with secretory IgA (SIgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating could be mediated by antigen-specific SIgA recognition, polyreactivity, and/or by the SIgA-associated glycans. In contrast to many in vitro studies, only a few reported the effect of SIgA glycans in vivo. Here, we used a germ-free antibody-free newborn piglets model to compare the protective effect of SIgA, SIgA with enzymatically removed N-glycans, Fab, and Fc containing the secretory component (Fc-SC) during oral necrotoxigenic E. coli O55 challenge. SIgA, Fab, and Fc-SC were protective, whereas removal of N-glycans from SIgA reduced SIgA-mediated protection as demonstrated by piglets' intestinal histology, clinical status, and survival. In vitro analyses indicated that deglycosylation of SIgA did not reduce agglutination of E. coli O55. These findings highlight the role of SIgA-associated N-glycans in protection. Further structural studies of SIgA-associated glycans would lead to the identification of those involved in the species-specific inhibition of attachment to corresponding epithelial cells.
- MeSH
- aglutinace MeSH
- Escherichia coli fyziologie MeSH
- glykosylace MeSH
- gnotobiologické modely MeSH
- imunoglobulin A sekreční metabolismus MeSH
- imunoglobuliny - Fab fragmenty metabolismus MeSH
- infekce vyvolané Escherichia coli imunologie MeSH
- jednořetězcové protilátky metabolismus MeSH
- novorozená zvířata MeSH
- odolnost vůči nemocem MeSH
- polysacharidy metabolismus MeSH
- prasata MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
strana 425-433 : ilustrace ; 24 cm
- MeSH
- B-lymfocyty MeSH
- Escherichia coli MeSH
- gnotobiologické modely MeSH
- imunita MeSH
- imunoglobuliny MeSH
- modely u zvířat MeSH
- prasata MeSH
- protilátky MeSH
- střevní sliznice MeSH
- Publikační typ
- klinická studie MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- alergologie a imunologie
- experimentální medicína
- NLK Publikační typ
- separáty