Browsing by Author "Bimczok, Diane"

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    Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells
    (2014) Das, Soumita; Sarkar, Arup; Ryan, Kieran A.; Fox, Sarah; Berger, Alice H.; Juncadella, Ignacio J.; Bimczok, Diane; Smythies, Lesley E.; Harris D., Paul R.; Ravichandran, Kodi S.; Crowe, Sheila E.; Smith, Phillip D.; Ernst, Peter B.
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    Human intestinal stromal cells promote homeostasis in normal mucosa but inflammation in Crohn's disease in a retinoic acid-deficient manner
    (2024) Smythies, Lesley E.; Belyaeva, Olga V.; Alexander, Katie L.; Bimczok, Diane; Nick, Heidi J.; Serrano, Carolina A.; Huff, Kayci R.; Nearing, Marie; Musgrove, Lois; Poovey, Emily H.; Garth, Jaleesa; Russ, Kirk; Baig, Kondal R. K. K.; Crossman, David K.; Peter, Shajan; Cannon, Jamie A.; Elson, Charles O.; Kedishvili, Natalia Y.; Smith, Phillip D.
    Intestinal stromal cells (SCs), which synthesize the extracellular matrix that gives the mucosa its structure, are newly appreciated to play a role in mucosal inflammation. Here, we show that human intestinal vimentin+CD90+smooth muscle actin- SCs synthesize retinoic acid (RA) at levels equivalent to intestinal epithelial cells, a function in the human intestine previously attributed exclusively to epithelial cells. Crohn's disease SCs (Crohn's SCs), however, synthesized markedly less RA than SCs from healthy intestine (normal SCs). We also show that microbe-stimulated Crohn's SCs, which are more inflammatory than stimulated normal SCs, induced less RA-regulated differentiation of mucosal dendritic cells (DCs) (circulating pre-DCs and monocyte-derived DCs), leading to the generation of more potent inflammatory interferon-gamma hi/interleukin-17hi T cells than normal SCs. Explaining these results, Crohn's SCs expressed more DHRS3, a retinaldehyde reductase that inhibits retinol conversion to retinal and, thus, synthesized less RA than normal SCs. These findings uncover a microbe-SC-DC crosstalk in which luminal microbes induce Crohn's disease SCs to initiate and perpetuate inflammation through impaired synthesis of RA.
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    Interactions between H. pylori and the gastric microbiome: impact on gastric homeostasis and disease
    (ELSEVIER, 2021) Serrano Honeyman, Carolina Andrea; Harris Diez, Paul Richard; Smith, Phillip D.; Bimczok, Diane
    Like many seemingly inhospitable environments on our planet, the highly acidic human stomach harbors a diverse bacterial microflora. The best-known member of the human gastric flora, Helicobacter pylori, causes a number of gastric diseases, including peptic ulcer disease and gastric adenocarcinoma. In the absence of H. pylori infection, the gastric microbiota displays some features similar to the oral cavity with Firmicutes the most common phylum, followed by Proteobacteria and Bacteroidetes. When present, H. pylori dominates the gastric microbiome and reduces diversity and composition of other taxa. The composition of the gastric microbiome also is altered in the setting of proton pump inhibitor therapy and gastric neoplasia. This review summarizes foundational and recent studies that have investigated the composition of the human gastric microbiome in a variety of patient groups, with a focus on potential mechanisms involved in regulation of gastric microbial community structure.
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    MNPmApp: An image analysis tool to quantify mononuclear phagocyte distribution in mucosal tissues
    (2022) Potts, Catherine; Schearer, Julia; Sebrell, Thomas A.; Bair, Dominic; Ayler, Becky; Love, Jordan; Dankoff, Jennifer; Harris, Paul R.; Zosso, Dominique; Bimczok, Diane
    Mononuclear phagocytes (MNPs) such as dendritic cells and macrophages perform key sentinel functions in mucosal tissues and are responsible for inducing and maintaining adaptive immune responses to mucosal pathogens. Positioning of MNPs at the epithelial interface facilitates their access to luminally-derived antigens and regulates MNP function through soluble mediators or surface receptor interactions. Therefore, accurately quantifying the distribution of MNPs within mucosal tissues as well as their spatial relationship with other cells is important to infer functional cellular interactions in health and disease. In this study, we developed and validated a MATLAB-based tissue cytometry platform, termed "MNP mapping application" (MNPmApp), that performs high throughput analyses of MNP density and distribution in the gastrointestinal mucosa based on digital multicolor fluorescence microscopy images and that integrates a Monte Carlo modeling feature to assess randomness of MNP distribution. MNPmApp identified MNPs in tissue sections of the human gastric mucosa with 98 ± 2% specificity and 76 ± 15% sensitivity for HLA-DR+ MNPs and 98 ± 1% specificity and 85 ± 12% sensitivity for CD11c+ MNPs. Monte Carlo modeling revealed that mean MNP-MNP distances for both HLA-DR+ and CD11c+ MNPs were significantly lower than anticipated based on random cell placement, whereas MNP-epithelial distances were similar to randomly placed cells. Surprisingly, H. pylori infection had no significant impact on the number of HLA-DR and CD11c MNPs or their distribution within the gastric lamina propria. However, our study demonstrated that MNPmApp is a reliable and user-friendly tool for unbiased quantitation of MNPs and their distribution at mucosal sites.