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Function of gut mucosal barrier: methodology and modulation.
Hornová, Michaela ; Tlaskalová - Hogenová, Helena (advisor) ; Prokešová, Ludmila (referee)
ABSTACT Function of gut mucosal barrier: methodology and modulation Right function of the intestinal barrier is essential for maintaining the homeostasis of the inner environment and it serves as a mechanical barrier against penetration of macromolecular compounds and microbes from outer environment. Impaired gut mucosa cannot effectively protect from invasion of infectious microorganisms, antigens from food, bacteria, viruses and xenobiotics into the subepithelial gut layer. Excessive interaction among the immune system and antigens from intestinal lumen can lead to immune mediated damage of the organism. Damaged intestinal barrier plays an important role in the pathogenesis of inflammatory and autoimmune diseases, like inflammatory bowel disease, diabetes, celiac disease and rheumatoid arthritis. The aim of this study was to define methods for measuring intestinal permeability, which would reflect the gut barrier damage. We were trying to detect the gut damage caused by indomethacin (non-steroidal anti-inflammatory drug), alcohol and bacterial LPS by measuring the intestinal permeability for 4,4 kDa FITC-dextran. We were also evaluating changes in gene expression of tight junction proteins, IL-6 and iNOS in mice after intraperitoneal administration of LPS, which induces septic shock. Another goal was to...
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Studying immune system using MHC II/ EGFP knock-in mouse
Zadražil, Zdeněk ; Černý, Jan (advisor) ; Tlaskalová - Hogenová, Helena (referee)
The immune system is essential for keeping the integrity of multicellular organisms. We were able to make a step forward in studying the complex immune reactions in mammals in vivo and/ or in situ using the major histocompatibility complex (MHC) class II/ enhanced green fluorescent protein (EGFP) knock-in mouse model. Due to the EGFP visualization of MHC II expressing cells we were able to observe antigen presenting cells, which are essential for the onset of immune responses, in their natural environment. Thus, we report some original features of the immune system. We have identified MHC II+ cell clusters with unknown, probably unique function, in the intestine. We have also described MHC II+ cell migration to the lactating mammary gland and tested few hypotheses about the role of this phenomenon for the development of the mammary gland, milk secretion or infant immune system establishment. Lastly, we observed residential macrophages in the cornea. The presence of APCs in the cornea is a very contradictory issue due to the fact that cornea is an immunologically privileged tissue and therefore harbors special immune features. key words: antigen presenting cells (APC), major histocompatibility complex class II (MHC II), enhanced green fluorescent protein (EGFP), immune system, knock-in mouse model
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The role of toll-like receptors in the pathogenesis of liver diseases
Petrášek, Jan ; Jirsa, Milan (advisor) ; Tlaskalová - Hogenová, Helena (referee) ; Červinková, Zuzana (referee)
Identifikační záznam: PETRÁŠEK, Jan. ÚLOHA TOLL-LIKE RECEPTORŮ V PATOGENEZI JATERNÍCH ONEMOCNĚNÍ. [The role of toll-like receptors in the pathogenesis of liver diseases]. Praha, 2010. 198s., Disertační práce. Univerzita Karlova v Praze, 1. lékařská fakulta, Laboratoř Experimentální Hepatologie IKEM. Vedoucí práce: Milan Jirsa. Abstrakt Společným jmenovatelem nejčastějších onemocnění jater je aktivace mechanismů vrozené imunity, které přispívají k rozvoji zánětu a poškození jaterního parenchymu. Klíčovou úlohu v rozvoji jaterního poškození hrají Toll-like receptory, jejichž charakterizace v posledním desetiletí vedla přehodnocení patofyziologie některých jaterních onemocnění. Předkládaná práce studuje význam alelických variant v genech kódujících proteiny Toll-like receptorové signální kaskády a mezibuněčné signalizace v patogenezi alkoholické nemoci jater, přináší nový pohled na probiotika v léčbě nealkoholické steatohepatitidy a nové poznatky o protizánětlivém působení interferonů I. typu u některých jaterních chorob. Abstract Recent reports suggest that majority of chronic and acute liver diseases share a significant degree of liver inflammation and injury attributable to innate immunity, activated through Toll-like receptors. Detailed characterization of Toll-like receptor sigaling cascades in the last...
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Bacterial components in experimental intestinal inflammation prevention and therapy
Kverka, Miloslav ; Tlaskalová - Hogenová, Helena (advisor) ; Šedivá, Anna (referee) ; Stříž, Ilja (referee)
Although strong protective immune response is essential for preventing invasion by pathogens, equivalent responses against antigens originating from commensal bacteria can lead to chronic inflammatory diseases, such as inflammatory bowel disease (IBD). Manipulating the mucosal immune responses with microbial antigens might be an excellent tool to IBD therapy or prevention. Our aim was to gain some insight into the regulation of the intestinal inflammation and to isolate bacterial immunomodulatory components that could be used in intestinal inflammation therapy and prevention. One particular mechanism of how healthy colon tissue regulates the inflammation during acute experimental colitis is through modulation of bioavailability of glucocorticoids (GCs) in gut mucosa. Here, we show that intestinal inflammation changes the local GC metabolism, which ultimately leads to decrease in inflammatory readiness of cells in the gut mucosa and in mesenteric lymph nodes. This pre-receptor regulation of GC function could represent an important homeostatic function of the gut mucosa. The actual triggers of intestinal inflammation in IBD seem to be either microbial dysbiosis or microbes with special "pathogenic" abilities, which both could be rectified by feeding with probiotics. Here, we report that oral feeding with live...
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The Role of Gut Microbiota and Lipopolysachaide Content of the Diet in the Development, Maturation and Function of the Immune System
Hrnčíř, Tomáš ; Tlaskalová - Hogenová, Helena (advisor) ; Prokešová, Ludmila (referee) ; Macela, Aleš (referee)
Mammals are essentially born germ-free but the epithelial surfaces are promptly colonized by astounding numbers of bacteria soon after birth. The most extensive microbial community is harboured by the distal intestine. The gut microbiota outnumbers ~10 times the total number of our somatic and germ cells. The hostmicrobiota relationship has evolved to become mutually beneficial. Studies in germfree mice have shown that gut microbiota is essential for the proper development of the immune system. The pivotal role of the innate immune system in the complex and dynamic host-microbiota interactions has become increasingly evident. The principal aims of the present study were: firstly, to determine whether LPS-rich sterile diet can promote maturation of the immune system in germ-free mice, secondly, to elucidate whether gut microbiota and LPS-rich sterile diet influence the LPS susceptibility, and finally, to investigate a role of the adaptive immunity in endotoxin shock. Our data clearly show that both live gut microbiota and LPS-rich sterile diet increase susceptibility to endotoxin shock. Further, we demonstrate that immunodeficient SCID mice, which lack mature B and T cells, are more sensitive to endotoxin shock than immunocompetent Balb/c mice. In addition, we show that not only live gut microbiota but also...
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Adjuvant Mucosal Immunization of Mice against inFluenza Virus
Zanvit, Peter ; Prokešová, Ludmila (advisor) ; Tlaskalová - Hogenová, Helena (referee) ; Kopecký, Jan (referee)
Influenza virus infections cause considerable morbidity and mortality in the world. Current immunization against influenza is provided using parenterally given influenza vaccines. These vaccines can induce good systemic immunity but they fail to induce a protective mucosal immunity. Because of persisting threat of new highly pathogenic influenza A subtypes development, a vaccination inducing intersubtypic cross-protection is desirable. The principal aims of the present study were: firstly, to explore the effect of Bacillus firmus (BF) and its delipidated form (DBF) as mucosal adjuvants for immunization via respiratory tract, secondly to test the potencial of BF and DBF to induce intrasubtypic and intersubtypic protection and finally to characterize the mechanism of adjuvant effect. (...) The mechanism of adjuvant effect was tested in NALT after intranasal immunization of mice by inactivated influenza virus type A, adjuvant alone (DBF) and by mixture of virus+DBF. We tested the expression of selected genes for cytokines, toll-like receptors and other genes participating in immune response by qPCR. Intranasally given DBF and mainly mixture virus+DBF induced expression of cytokines characteristic for Th1 immune response (IFN-and IL-2) whereas expression of genes characteristic for Th2 was decreased (IL-4)....
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Gut microbiome and colorectal cancer
Tlaskalová-Hogenová, Helena ; Klimešová, Klára ; Zákostelská, Zuzana ; Kverka, Miloslav ; Hornová, Michaela ; Vannucci, Luca ; Štěpánková, Renata ; Hudcovic, Tomáš ; Kozáková, Hana ; Rossmann, Pavel
The work deals with metagenomic approaches that 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 microbiota on the host.
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