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Role of microbiota in mouse experimental model of psoriasis
Jirásková Zákostelská, Zuzana ; Stehlíková, Zuzana ; Klimešová, Klára ; Rossmann, Pavel ; Dvořák, Jiří ; Novosádová, Iva ; Kostovčík, Martin ; Coufal, Štěpán ; Šrůtková, Dagmar ; Hudcovic, Tomáš ; Štěpánková, Renata ; Rob, F. ; Jůzlová, P. ; Herzogová, J. ; Tlaskalová-Hogenová, Helena ; Kverka, Miloslav
Anotace v anglickém jazyce\n\nMouse model of human psoriasis and gnotobiotic are important tools in understanding the role of gut and skin microbiota in pathogenesis of psoriasis. In our experiments we showed that gnotobiotic mice, as well as conventional mice treated with antibiotics, have milder skin inflammation in comparison with control conventional mice. Treatment with broad spectrum antibiotics led to dramatic shift in gut microbial composition, in particular, we observed extensive increase of order Lactobacillales. To analyze the potential effect of Lactobacillales on skin inflammation, we further monocolonized mice with L. plantarum WCFS1. Also monocolonized mice showed lower skin inflammation in comparison with conventional mice. To understand whether microbial dysbiosis is cause or effect of psoriasis needs to be further investigated.\n\n
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Immunological markers for type 1 diabetes prediction
Včeláková, Jana ; Štechová, Kateřina (advisor) ; Černá, Marie (referee) ; Kverka, Miloslav (referee)
5 Abstract Type 1 diabetes (T1D) is an organ specific autoimmune disorder characterised by the immune-mediated destruction of insulin-producing pancreatic beta cells. Beta-cell destruction is mediated primarily by cellular components of the immune system, especially auto-reactive T cells. Nowadays, a goal of many studies is built up the best system for identification of individuals in prediabetes stage and to treat them to preserve sufficient amount of insulin producing beta cells. We identified several candidate pathways and proteins which could be important in pathology of T1D, like an antiviral responses and differentiation of Th17 pathways. We observed differences in dendritic cells count and in their cytokines production. Our data support the notion that the establishment of proinflammatory environment in genetically predisposed individuals along with the involvement of non-specific immune mechanisms is critical for the initiation of autoimmune, destructive insulitis. Nonetheless, patient's autoantibody profile reflects the type of cellular immune response and should be take in a count as well. This finding may be useful in design of immunointervention studies to prevent T1D. Considering the heterogeneity of the clinical course of this disease and perhaps different mechanisms of molecular pathology,...
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Role slizniční imunity a střevní mikroflóry při vývoji zánětlivých onemocnění
Málková, Jana ; Kverka, Miloslav (advisor) ; Bártová, Jiřina (referee)
Gut microbiota is important for our health and well-being, but when its composition is disrupted, it can induce or perpetuate several chronic inflammatory disorders, including inflammatory bowel diseases (IBD). The mechanisms which distinguish protective microbes from the deleterious or indifferent ones are largely unknown. The aim of this thesis was to study the interaction of the immune system with microbes that have different relationships to IBD pathogenesis. Escherichia coli is a predominant aerobic microorganism of the gastrointestinal tract. This species includes microbes implicated in induction of IBD as well as in its therapy. Four E. coli strains with different relations to IBD were selected for our experiments: E. coli Nissle 1917 (EcN), which has been successfully used in IBD therapy, E. coli strains LF82 and p19A, which have been implicated in the pathogenesis of IBD, and E. coli strain K6, which has neither been implicated in pathogenesis nor in protection from this disease. The experiments were performed both with living bacteria and inactivated ones. As the mode of inactivation may change the microbial antigenic structure, we measured how different methods of inactivation, i.e. 1% formaldehyde, exposure to heat or UV irradiation, influence the microbe's immunogenicity. First, we...
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Gut barrier function in pathogenesis of necrotizing enterocolitis
Coufal, Štěpán ; Kverka, Miloslav (advisor) ; Vančíková, Zuzana (referee)
Abstract Necrotizing enterocolitis (NEC) is severe and life-threatening disease of infant gastrointestinal tract (GIT). It is a defect of GIT adaptation to extrauterine life, which affects mostly premature infants and infants afflicted by congenital developmental defects of GIT or heart. Gut barrier disruption and presence of abnormal gut microbiota has eminent role in NEC pathogenesis. Nowadays, the diagnosis of NEC is based on presence of clinical symptoms - abdominal distension, blood in stool and radiologic finding Pneumatosis intestini. However, the symptoms are in early stage of NEC non- specific and do not allow unambiguous distinguishing of NEC from other GIT disorders or sepsis. Aim of this thesis was to extend the understanding of inflammatory response in neonates with NEC and to find applicable biomarker for early diagnosis of NEC and thereby provide quick intervention. Cytokines have important role in immune response regulation. Although the connection between some cytokines and NEC was described, the inflammatory response during NEC was not yet properly stated. The levels of 40 cytokines related to inflammation was shown in this thesis. Intestinal - Fatty Acid Binding Protein (i- FABP) is a small...
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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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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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