Publications by authors named "Vesselin Tomov"

A duodenal-cecal fistula is characterized as an unnatural connection between the duodenum and cecum. Here, we present the case of a 40-year-old male with unintentional weight loss and a history of foreign body ingestion a few years prior. Computerized tomography (CT) small bowel enterography showed a linear soft tissue tract extending from the inferior aspect of the distal duodenum to the cecum.

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The intestinal epithelium is a key physical interface that integrates dietary and microbial signals to regulate nutrient uptake and mucosal immune cell function. The transcriptional programs that regulate intestinal epithelial cell (IEC) quiescence, proliferation, and differentiation have been well characterized. However, how gene expression networks critical for IECs are posttranscriptionally regulated during homeostasis or inflammatory disease remains poorly understood.

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Background & Aims: Exhaustion of CD8 T cells has been suggested to inform different clinical outcomes in Crohn's disease, but detailed analyses are lacking. This study aimed to identify the role of exhaustion on a single-cell level and identify relevant CD8 T cell populations in Crohn's disease.

Methods: Blood and intestinal tissue from 58 patients with Crohn's disease (active disease or remission) were assessed for CD8 T cell expression of exhaustion markers and their cytokine profile by highly multiplexed flow and mass cytometry.

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The developmental origins of memory T cells remain incompletely understood. During the expansion phase of acute viral infection, we identified a distinct subset of virus-specific CD8 T cells that possessed distinct characteristics including expression of CD62L, T cell factor 1 (TCF-1), and Eomesodermin; relative quiescence; expression of activation markers; and features of limited effector differentiation. These cells were a quantitatively minor subpopulation of the TCF-1 pool and exhibited self-renewal, heightened DNA damage surveillance activity, and preferential long-term recall capacity.

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Background & Aims: Noroviruses (NoVs) are the leading cause of acute gastroenteritis worldwide and are associated with significant morbidity and mortality. Moreover, an asymptomatic carrier state can persist following acute infection, promoting NoV spread and evolution. Thus, defining immune correlates of NoV protection and persistence is needed to guide the development of future vaccines and limit viral spread.

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Simultaneous analyses of peripheral and mucosal immune compartments can yield insight into the pathogenesis of mucosal-associated diseases. Although methods to preserve peripheral immune cells are well established, studies involving mucosal immune cells have been hampered by lack of simple storage techniques. We provide a cryopreservation protocol allowing for storage of gastrointestinal (GI) tissue with preservation of viability and functionality of both immune and epithelial cells.

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Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8 T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8 T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion.

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A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions.

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The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching.

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In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication.

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Article Synopsis
  • The mammalian intestine houses beneficial bacteria and is also affected by pathogens, including helminth parasites, which can modulate immune responses.
  • In a study of virus-helminth coinfection, helminths were found to weaken antiviral immunity and alter the gut microbiota, alongside macrophage activation dependent on the STAT6 pathway.
  • Interestingly, even in the absence of microbiota (germ-free mice), helminth-induced immune impairment was observed, but blocking a specific molecule, Ym1, could help restore some antiviral function, indicating the immunomodulatory effects of helminths are primarily mediated by Ym1 rather than changes in microbiota.
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Background: There is a need for simple, noninvasive patient-driven disease assessment instruments in ulcerative colitis (UC). We sought to further assess and refine the previous described 6-point Mayo score.

Methods: A cross-sectional study of 282 UC patients was conducted assessing the correlation of the 2 patient-reported Mayo score components (6-point Mayo score) with the simple clinical colitis activity index (SCCAI) and a single Likert scale of patient-reported disease activity.

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Article Synopsis
  • Norovirus (NV) gastroenteritis significantly impacts global health, and the study explores how T cells help in controlling the murine norovirus (MNV) infection.
  • Researchers identified a key MNV-specific epitope, which revealed the dynamic behavior of CD8 T cells in the intestinal mucosa, particularly during infections with different MNV strains.
  • The study found that while acute infections triggered a strong T cell response, chronic infections resulted in fewer and less-effective CD8 T cells, emphasizing their role in antiviral immunity in the intestines.
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The identification of host cell factors for virus replication holds great promise for the development of new antiviral therapies. Recently, high-throughput screening methods have emerged as powerful tools to identify candidate host factors for therapeutic intervention. The development of assay systems suitable for large-scale automated screening is of particular importance for novel viruses with high pathogenic potential for which limited biological information can be developed in a short period of time.

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