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.

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 from patients, 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 (Hoffmanová I, et al. 2015, Sánchez D, et al. 2016). The original findings of our studies are disseminated via a teaching activity (Theory of immunology methods; Faculty of Science, Charles University in Prague).

Next, we linked our interest in early diagnostics with our long-time passion for host-microbe interaction and start to study the predictive capacity of anti-microbial response and biomarkers of gut damage in multiple human diseases. We focused on intestinal fatty acid binding protein (I-FABP), which is released to the bloodstream, and later filtered to the urine, as a result of gut epithelium damage. We found that analysis of urinary I-FABP could not only predict the post-operative neonatal necrotizing enterologitis (NEC), but it can also distinguish it from sepsis (Coufal et al., 2016). We continued our research with other neonatal emergencies finding that while I-FABP is a marker for intestinal mucosa damage in gastroschisis, it fails to predict early recovery, so it is not suitable for outcome prediction in clinical settings (Kokesova et al., 2019). Next, to gain an insight into the inflammatory bowel disease (IBD) pathogenesis, we analyzed serum biomarkers and specific anti-microbial B and T cell responses to the gut commensals in different forms of IBD. We found that decrease in matrix metalloproteinase (MMP)-9 and increase in MMP-14 are the strongest factors discriminating IBD patients from healthy subjects and that low transforming growth factor-β1 (TGF-β1) is associated with disease relapse and low osteoprotegerin with anti-tumor necrosis factor-alpha (TNF-α) therapy. Patients with CD have significantly decreased antibody and increased T cell response mainly to genera Eubacterium, Faecalibacterium and Bacteroides. These results stress the importance of the gut barrier function and immune response to commensal bacteria and point at the specific differences in pathogenesis of different forms of IBD (Coufal et al., 2019).

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