Tanya Dimova

Institute of Biology and Immunology of Reproduction "Acad. Kiril Bratanov" · Immunobiology of reproduction

Problem Human implantation is a limiting factor for the success of natural and IVF reproduction since about 60% of pregnancy losses occur in the peri‐implantation period. The in vitro modeling of human implantation challenges the researchers in accurate recreation of the complex in vivo differentiation and function of human blastocyst in the peri‐i...

Study question Are the in vitro developed 3D-Sw71 blastocyst-like model and the primary trophoblast 3D model interchangeable? Summary answer We confirmed that 3D-Sw71 model can be successfully replaced by 3D primary trophoblast model. What is known already Overcoming the challenges and ethical considerations of manipulating human embryos, researc...

An efficient immune defense against pathogens requires sufficient basal sensing mechanisms that can deliver prompt responses. Type I IFNs are protective against acute viral infections and respond to viral and bacterial infections, but their efficacy depends on constitutive basal activity that promotes the expression of downstream genes known as IFN...

Yersiniosis is the third most commonly reported foodborne zoonosis in the European Union. Here, we evaluated the prevalence of pathogenic Yersinia enterocolitica among healthy pigs (as a major reservoir) in a slaughterhouse in Bulgaria. A total of 790 tonsils and feces from 601 pigs were examined. Isolation and pathogenicity characterization was ca...

Problem: Long-lived mycobacterial L-forms (mL-forms) could be detected in the blood of BCG-vaccinated people. We have previously found mL-forms in term placentas and blood of neonates, delivered by healthy BCG-vaccinated mothers as first formal demonstration that BCG vaccination in the childhood of the woman could affect her placentobiome during p...

Human γδ T cells are enriched at the maternal-fetal interface (MFI, decidua basalis) showing a highly differentiated phenotype. However, their functional potential is not well-known and it is not clear whether this decidua-enrichment is associated with specific γδ T cell receptors (TCR) as is observed in mice. Here we addressed these open questions...

Both KIR and HLA are the most variable gene families in the human genome. The recognition of the semi‐allogeneic embryo‐derived trophoblasts by maternal decidual NK (dNK) cells is essential for the establishment of the functional placenta. This recognition is based on the KIR‐HLA interactions and trophoblast expresses a specific HLA profile that co...

In healthy couples over half of the conceptions result in failed pregnancy and around 30% of them occur during implantation defining it as a rate-limiting step for the success of native and in vitro fertilization. The understanding of the factors regulating each step of implantation and immune recognition is critical for the pregnancy outcome. Crea...

In this study we used FACS analysis, in vitro stimulation of pathogen-reactive γδ T cells with placenta-derived mL-forms, rats challenge experiments with in vivo inoculation of such mL-forms and scanning electron microscopy (SEM). Only L-forms genetically identified as mycobacterial (Mycobacterium bovis BCG), based on specific IS6110 TagMan qPCR we...

Novel 3D cell models – surrogates from human cell lines as a modern, non-invasive, ethical approach to mimic human embryo behavior in the earliest peri-implantation period. Presented at Sofia science festival 2021.

PROBLEM: Although the paternal antigens can cause severe NK-and T-cell responses by the maternal immune system, the semi-allogeneic fetus is not usually rejected suggesting active mechanisms of immune tolerance and/or fetus escape strategy. Such one is the atypical expression of HLA molecules by the extravillous trophoblast cells (EVT) in contact w...

In this chapter, human unconventional γδT lymphocytes and their major subsets will be described with emphasis on their role in the immune protection in general and in the context of pregnancy. In particular, I will outline the main events and immune cells at the maternal-fetal interface during implantation/early pregnancy in humans focusing on the...

Significance Early-life immune responses have been described as suboptimal, with neonates and infants being susceptible to infections. Vγ9Vδ2 T cells are the first T lymphocytes to be generated in the human fetus. Their T cell receptor-mediated responses to in vitro stimulation and their effector functions at birth are weaker compared with those in...

Problem: A successful outcome to pregnancy is critically dependent on the initiation of maternal immune tolerance before embryo implantation. Cells of embryonic origin that come in contact with the uterine microenvironment can exert influence over the phenotype and function of immune cells to facilitate robust implantation, however what influence...

: Pregnancy is a state where high and stage-dependent plasticity of the maternal immune system is necessary in order to equilibrate between immunosuppression of harmful responses towards the fetus and ability to fight infections. TCR γδ cells have been implicated in the responses in infectious diseases, in the regulation of immune responses, and in...

At the crossroad between Europe, Asia and Africa, Bulgaria is part of the Mediterranean/Black Sea Flyway (MBSF) used by millions of migratory birds. In this study bird species migrating through Bulgaria were investigated as carriers of zoonotic pathogens. In total, 706 birds belonging to 46 species were checked for the presence of various bacterial...

The ability of bacteria to exist as a population of self-replicating forms with defective or entirely missing cell wall (L-forms) is an adaptive mechanism for their survival and reproduction under unfavorable conditions. Bacterial mother-to-fetus transfer is a universal phenomenon in the animal kingdom. However, data about vertical transfer of L ba...

Our previous studies showed that mycobacterial L-forms persist in the blood of BCG vaccinated people and that BCG vaccine is able to produce, under appropriate conditions, filterable, self-replicating L-bodies with virus-like size. Because filterability is one of the characteristics of L-forms, considerable interest has been shown in their capacity...

Significance Despite their enormous potential for diversity (in excess of 10 ¹⁵ theoretical receptor specificities), the human γδ T-cell repertoire is dominated by a specific subset expressing the T-cell receptor containing the γ-chain variable region 9 and the δ-chain variable region 2 (Vγ9Vδ2) known to react to a set of pathogen-derived small mol...

Regulatory T cells (Treg cells), a small subset of CD4(+) T cells maintaining tolerance by immunosuppression, are proposed contributors to the survival of the fetal semiallograft. We investigated Treg cells in paired decidual and peripheral blood (PB) samples from healthy women in early pregnancy and PB samples from non-pregnant women. Distribution...

The immune system in early life is regarded as immature. However, the IL-12 family member IL-23 is highly produced upon TLR stimulation by neonatal DCs. Human adult Vγ9Vδ2 T cells can be stimulated specifically via their TCR by phosphoantigens (as the pathogen-derived HMB-PP) or agents and infections that lead to their endogenous accumulation (as t...

Different strategies for implantation in the mammals require specific endometrial remodelling as well as the predominance of certain immune cell populations. Here we aimed to follow up the dynamics of endometrium-based inflammatory cells - eosinophils and monocyte/macrophages - in respect to the phase and place of implantation. The study was perfor...

The uniqueness of the human placenta cannot be replaced by animal models. In vitro studies are compulsory to elucidate the biology of human placenta and require isolation and purification of villous trophoblasts, which can be used in molecular and functional studies. Constant improvement in the isolation technique is required to obtain a high yield...

We evaluated implantation-associated quantitative changes in endometrial and peripheral natural killer (NK)-cell populations of pigs. Natural killer cell populations were investigated in 10, 15, 20, 30 and 40 days pregnant and non-pregnant (NP) sows by flow cytometry, immunohistochemistry and morphometry. The number of endometrial CD16(+) NK cells...

We assessed implantation-associated quantitative changes in peripheral blood and endometrial T lymphocytes throughout epitheliochorial placenta formation. T-cell subsets were investigated in 10-, 15-, 20-, 30-, and 40-day pregnant and non-pregnant sows by flow cytometry and immunohistochemistry. Endometrial total T, T cytotoxic (Tc), and T helper (...