Laboratory of cellular and molecular immunology

The Laboratory of Cellular and Molecular Immunology investigates the interactions between host and microbes in relation to host function and/or health. The involvement of the microbiome in the development or maintenance of diseases is studied in animal models such as conventional or germ-free mice, but also in human patients, thanks to collaborations with major medical institutions involved in applied research on human diseases. Major diseases studied in the context of the microbiome include inflammatory bowel disease, eating and sleep disorders, autoimmune uveitis, multiple sclerosis, Parkinson´s disease, lymph node tumors and atopic dermatitis. The investigation of adaptive immune mechanisms is then focused on autoimmune diseases such as coeliac disease and type 1 diabetes.

The laboratory is focused on three main topics: (1) mucosal immunity and host-microbe interactions in inflammatory diseases and cance; (2) the influence of the microbiota on mental health; (3) investigation of the influence of environmental factors in autoimmune diseases - coeliac disease, food allergy and type 1 diabetes.

1)    Mucosal immunity and host-microbe interactions in inflammatory diseases

The main research areas of the laboratory are innate and adaptive immunity on mucosal surfaces. Host-microbe interactions influence the physiological functions of the host. Many multifactorial diseases result from an impaired mucosal barrier or altered immune responses to components of the gut microbiota. Influencing the gut microbiota through diet, drugs or the disease can therefore make a person more susceptible or resistant to immune-mediated diseases such as inflammatory or autoimmune diseases or cancer. Metabolites of the gut microbiota influence the maturation and activity of T cells and can regulate the host's immune system. The microbes on the intestinal epithelium regulate the immune response of T cells in the gut, and different diets can influence the host's resistance to inflammation in the gut by affecting either the local pro-inflammatory environment or the function of the intestinal barrier.
The gut microbiota controls the maturation of the immune system and regulates its function throughout life. However, the host immune system responds differently to antimicrobial or nutritional stimuli at different developmental stages, which is why we focus on analyzing the interactions between host, microbiota and nutrition during the early developmental window of opportunity. Therefore, the microbes in a particular organ (e.g. the gut or skin) not only have an impact on the health of that organ, but also on distant tissues and other organs. Therefore, in the laboratory we analyze the phenotype of immune cells infiltrating healthy or inflamed tissue and determine the movement of cells between inducer and effector sites of the mucosal immune system as well as the movement of cells between the gut and distant tissues.
As part of this research focus, we are also investigating the changes in microbial activity caused by extreme diets and the resulting phenotype changes in inflammatory and cancer diseases. We also study the role of the microbiome in the development of atopic dermatitis and food allergies in infants, in the efficacy of cancer therapies, in autoimmune uveitis, in the efficacy of immunomodulatory therapies and in the pathogenesis of multiple sclerosis and in many other serious human diseases.

2) The influence of the microbiota on mental health

Not only the intestinal tract of the host itself, but also the microbiota present can influence the function of the central nervous system. The bidirectional interaction between the gut and the brain via the brain-gut-microbiota axis involves neuronal, hormonal and immunological communication. The microbiota interacts with the vagus nerve, which connects the brain to the entire gastrointestinal tract. The afferent fibers of the vagus can sense signals from the microbiota via bacterial compounds and metabolites produced by dietary components such as SCFAs, secondary bile acids and tryptophan metabolites. These molecules signal by interacting with enteroendocrine and enterochromaffin cells of the digestive tract. Gut microbes also influence immune cells and possible inflammation, which can indirectly affect the brain. In addition, bacteria can produce neuroactive compounds such as γ-aminobutyric acid (GABA), serotonin, dopamine, acetylcholine and noradrenaline, which act locally on the enteric nervous system. Neurotransmitters can pass through the intestinal mucosa and enter the bloodstream, but are generally unable to cross the blood-brain barrier and have a more indirect effect on the enteric nervous system. Microbiota-free animals provide compelling evidence of a link between the microbiota and the brain, as the brain and the entire central nervous system show deviations from normal development. An altered microbiome can therefore influence mental health, stress, anxiety and depression.
Since diet is one of the most important factors shaping the composition of the gut microbiome, it is not surprising that people with eating disorders such as anorexia nervosa, bulimia nervosa or psychogenic overeating have an altered composition of the gut microbiome. The differences in the composition of the gut microbiome in people with anorexia nervosa are a consequence of starvation, where microorganisms equipped with mechanisms to grow at lower energy levels survive and dominate the competitive situation in the gut. Altered composition of the gut microbiome due to diet and stress can lead to impaired gut barrier function, passage of microbial components through the gut barrier and into the bloodstream, and subsequent activation of the immune system and inflammatory response.
In our lab, we aim to elucidate the role of the gut microbiota in the development and maintenance of eating disorders and identify the mechanisms of action of specific relevant microorganisms, as the gut microbiota and its influence on human physical and mental health may be a missing element in understanding the etiology of eating disorders..

3) Investigation of the influence of environmental factors in autoimmune diseases - coeliac disease, food allergy and type 1 diabetes

The antibody response against antigens and autoantigens is an essential component of adaptive immune mechanisms. However, the effects of the antibodies produced on human health are pleiotropic and depend on their heterogeneity, i.e. isotype ratio, specificity and affinity. The role of different antibodies and autoantibodies is not clear, but the presence of certain antibodies in serum may have diagnostic value. In collaboration with physicians, we are investigating antibodies against gliadin and other food proteins as well as autoantibodies in patients with active celiac disease, in patients on a gluten-free diet, in patients with autoimmune diseases associated with celiac disease and in the general population. Another topic currently under investigation is the gluten-free diet for the prevention of type 1 diabetes and its effects on motor and cognitive symptoms as well as innate and adaptive immunity in Parkinson's disease.

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