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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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Identification of new virulence factors in intracellular pathogen Francisella tularensis
Daňková, Věra ; Szotáková, Barbora (advisor) ; Krejsek, Jan (referee) ; Prokešová, Ludmila (referee)
ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Věra Daňková Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of Doctoral Thesis: IDENTIFICATION OF NEW VIRULENCE FACTORS IN INTRACELULLAR PATHOGEN FRANCISELLA TULARENSIS This dissertation thesis is focused on the role of bacterial tetratricopeptide repeat-like (TPR-like) proteins in the pathogenesis of infection. As a model organism we have chosen highly virulent intracellular bacterium Francisella tularensis (F. tularensis), whose mechanism of pathogenesis is not completely described. In the first part of dissertation thesis we took advantage of bioinformatic methods and identified three genes (FTS_0201, FTS_1680, and FTS_0778) with predicted TPR-like domains. Mutants defective in protein expression were prepared by TargeTron insertion mutagenesis. Prepared mutant strains were used for studying the role of selected proteins in pathogenicity and immunogenicity of F. tularensis subsp. holarctica strain employing in vivo and in vitro models and further for studying the involvement of these proteins in stress tolerance. Our results showed that the FTS_1680 protein is required for intracellular replication and full virulence of bacterium. We also described impaired ability...
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Immune response of mouse respiratory tract after immunization with influenza virus
Berková, Veronika ; Prokešová, Ludmila (advisor) ; Tučková, Ludmila (referee)
Immune response of mice after mucosal immunization by influenza virus type A with bacterial adjuvant Bacillus firmus Immunization of mice by inactivated influenza virus via respiratory tract induces a good mucosal and systemic immune response if bacterial adjuvant - delipidated G+ non- pathogenic bacterium Baccillus firmus (DBF) - is used. BALB/c mice were immunized intratracheally (IT) or intranasally (IN) with inactivated influenza A/PR/8/34 virus in combination with adjuvant DBF (50, 100, 200 or 500μg per immunization dose). We tested the production of antibodies against homologous virus and cross-reacting antibodies against subtype H3N2, H6N2 and H9N2 viruses in serum and mucosal secretions of nose, lungs and intestine by the ELISA method. Immunization of mice with virus itself induces the production of antibodies against homologous virus and lower production of cross-reacting antibodies against heterologous subtypes. Immunostimulatory adjuvant activity (optimal 100μg per immunization dose) enhances systemic and mucosal antibody production against homologous virus (H1N1) and markedly against heterologous subtypes (H3N2, H6N2, H9N2), especially after IT immunization of mice. For evaluation of cellular immunity, we tested spleen cell proliferation of immunized mice by 3 H-thymidine incorporation and...
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Role of bacteria and mucosal immune system and their interaction in the pathogenesis of inflammatory bowel disease
Du, Zhengyu ; Hudcovic, Tomáš (advisor) ; Prokešová, Ludmila (referee) ; Kamanová, Jana (referee)
Although the etiology and pathogenesis of inflammatory bowel disease (IBD) is not fully understood, it is generally accepted that the inflammation results from aberrant immune responses to antigens of gut microbiota in genetically susceptible individuals (Sartor et al., 2006). Alteration in intestinal microbiota has been found in IBD patients with increased abundance of certain bacteria and decreased abundance of others. Due to the complexity of the disease, multifaceted interactions between genetic factors, host immune response, gut microbiota and environment factors need to be taken into account. In this thesis, the pathogenesis of IBD was first reviewed in respect with the four factors mentioned above. Then we concentrated on the interaction between IBD-associated bacteria and mucosal immune system. We investigated the ability of mucosal-associated bacteria (MAB) from IBD patients to induce spontaneous colitis in germ-free (GF) mice and the impact of those bacteria on the development of dextran sulfate sodium (DSS)-colitis. Together with the analysis of the composition of gut microbiota of MAB colonized mice, we demonstrated the potential deleterious microbes were able to increase the susceptibility to DSS-colitis once they found a suitable niche. We revealed the mechanism of an E.coli strain...
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Mucosal immunity in upper respiratory tract diseases and autoimmunity diseases
Fundová, Petra ; Tlaskalová - Hogenová, Helena (advisor) ; Prokešová, Ludmila (referee) ; Bártová, Jiřina (referee)
Mucosal immune system comprises not only the major compartment of the immune system but also important interface with the outer environment. It is responsible in maintaining an intricate balance with the danger and non-danger stimuli of the outer world by employing specific anatomical features and unique functional mechanisms. Mucosal immune system has been long understudied, perhaps due to the limited accessibility, and its biological importance is thus still underevaluated. However, it has become evident that it is important to study mucosal immune system not only in local mucosal affections but also when uncovering pathogenic mechanisms and novel prevention strategies of organ specific autoimmune diseases such as type 1 diabetes. Thus, the first, more clinically oriented part of this thesis is focused on mucosal immune system of the upper respiratory tract in disease conditions - in nasal polyposis (NP). Because there is a substantial accumulation of eosinophils and neutrophils in the most frequent type of NP, we investigated and described increased expression of chemokine receptors CCR1 and CCR3 in NP versus nasal mucosa. Both innate immune mechanisms as well as homeostasis of epithelial cells may participate in NP. We have documented increased numbers of iNOS-positive and insulin-like growth...
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