The Czech Academy of Sciences, Institute of Microbiology, v.v.i.

LABORATORY OF CELLULAR AND MOLECULAR IMMUNOLOGY

Videnska 1083, 142 20 Prague-4, Czech Republic

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Laboratory of cellular and molecular immunology

The Laboratory is focused on three main topics: (i) comparative immunology, isolation and characterization of new molecules in defense mechanisms in the evolution; (ii) the study of  autoimmune diseases – celiac disease and  type 1 diabetes, the effect of environmental factors; (iii) mucosal immunity and host microbe interactions in inflammatory diseases and cancer.







Comparative immunology

To study the comparative and developmental immunity, we use quite unusual model organism, earthworm Eisenia andrei, which lives mostly in compost representing the environment with very high antigenic pressure. In contrast to sophisticated vertebrate or mammalian immune system, the use of invertebrate organism is, due to its simplicity, appropriate for the study of various aspects of innate immunity. Since invertebrates do not possess the acquired immunity, earthworms rely solely on the innate immunity in their defense strategies. The coelomic fluid of earthworms contains a great variety of molecules involved in direct elimination of invading microorganisms. We have identified several of such molecules, e.g. pattern recognition receptors – coelomic cytolytic factor, two Toll-like receptors and LBP/BPI molecule. These receptors recognize various conserved molecular structures of microorganisms. The highest abundancy of these molecules is present in the intestine representing the tissue in direct contact with microorganisms. Further, we have described some antimicrobial proteins such as lysozyme and lysenin/fetidin molecules.
Earthworms participate in soil fertility. They are in very close contact with the soil via both alimentary tract and highly permeable skin. They have been described to bioaccumulate various organic and inorganic pollutants and thus allow these substances to enter the food chain. For these reasons, earthworms are often used in monitoring soil ecotoxicity. In our laboratory, we follow the defense response of earthworms on various organic pollutants and also nanoparticles.

The aims of our research group are:
•    Recognition and description of novel molecules involved in defense reactions of earthworms. Assessment of their role in terms of developmental immunity and defense responses in vertebrate and mammals.
•    Isolation of biologically active compounds with possible applications in laboratories and pharmaceuticals. 
•    Finding potential sensitive earthworm biomarkers as tools for soil pollution assessment.






Gut microbiota and inflammatory diseases

To study the mucosal immunology and host-microbe interactions, we are focused mainly on the gut. Gut microbiota is a complex ecosystem consisting of vast number of bacteria, viruses, and fungi that have not been fully characterized. Numerous host-microbe interactions are shaping the microbial community and influence host's physiological functions, development of the immune system, and provoke various pathological conditions. Many multifactorial disorders occur as consequence of the disturbed mucosal barrier or as the results of alterations in the immune response to the components of gut microbiota. Therefore, by shaping the gut microbiota by diet, drugs or disease itself the individual may became more susceptible to the immune-mediated diseases such as inflammatory or autoimmune diseases or cancer. We study this interaction to gain deeper understanding of the underlying mechanisms. By combining the aproaches of basic research with analysis of samples frompatients , we try to translate this knowledge into clinical practice. The effect of gut microbiota is not limited only to typical diseases of the gut, such as inflammatory bowel disease, but it may influence the skin inflammation during psoriasis, lung inflammation in asthma or eye inflammation in autoimmune uveitis. Here, we study which microbes are associated with these diseases and their complications and how these microbes interact with the host in order to improve the diagnostic, therapy or even prevention.






Biomarkers of human diseases

Antibody response against antigens and self-antigens is an integral part of adaptive immune mechanisms. However, the somatic effect of generated antibodies is pleiotropic, depending on their heterogeneity, i.e. the ratio of isotypes, specificity and affinity. In consistence with this fact, the role of various antibodies and autoantibodies is a matter of contention due to the absence of a clinical correlate. Nevertheless, the occurrence of certain serum antibodies is of diagnostic value.  Notably, the testing of specific antibody may possess a promising prognostic or predictive potential. For this reason, in cooperation with physicians we focused on the study of antibody response against gliadins and other food-proteins and autoantibodies in patients with active celiac disease, those on a gluten-free diet, patients with autoimmune disease associated with celiac disease, and in general population. Moreover, we also studied the occurrence of autoantibodies against the multifunctional protein calreticulin, their heterogeneity and fine specificity and clinical relevance in patients with autoimmune and oncological diseases and idiopathic cardiomyopathies. The original findings of our studies are disseminated via a teaching activity (Theory of immunology methods; Faculty of Science, Charles University in Prague).

Coufal S, et al. Urinary Intestinal Fatty Acid-Binding Protein Can Distinguish Necrotizing Enterocolitis from Sepsis in Early Stage of the Disease. J Immunol Res. 2016;2016:5727312.

Sánchez D, et al. Anti-calreticulin antibodies and calreticulin in sera of patients diagnosed with dilated or hypertrophic cardiomyopathy. Autoimmunity. 2016 Dec;49(8):554-562.

Hoffmanová I, et al. Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2. Physiol Res. 2015 Aug 20;64(4):537-46.



















  
Czech Republic
Czech Immunological Society
Institute of Microbiology of the CAS The Czech Academy of Sciences
Czech republic CIS IMIC CAS





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