{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T11:33:57Z","timestamp":1770464037435,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["DFG GRK 2318\/1-318905415"],"award-info":[{"award-number":["DFG GRK 2318\/1-318905415"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["DFG TRR 241-375876048 (B06)"],"award-info":[{"award-number":["DFG TRR 241-375876048 (B06)"]}]},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin","award":["DFG GRK 2318\/1-318905415"],"award-info":[{"award-number":["DFG GRK 2318\/1-318905415"]}]},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin","award":["DFG TRR 241-375876048 (B06)"],"award-info":[{"award-number":["DFG TRR 241-375876048 (B06)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Based on indirect evidence, increased mucosal translocation of gut-derived microbial macromolecules has been proposed as an important pathomechanism in HIV infection. Here, we quantified macromolecule translocation across intestinal mucosa from treatment-naive HIV-infected patients, HIV-infected patients treated by combination antiretroviral therapy, and HIV-negative controls and analyzed the translocation pathways involved. Macromolecule permeability was quantified by FITC-Dextran 4000 (FD4) and horseradish peroxidase (HRP) flux measurements. Translocation pathways were addressed using cold inhibition experiments. Tight junction proteins were characterized by immunoblotting. Epithelial apoptosis was quantified and translocation pathways were further characterized by flux studies in T84 cell monolayers using inducers and inhibitors of apoptosis and endocytosis. In duodenal mucosa of untreated but not treated HIV-infected patients, FD4 and HRP permeabilities were more than a 4-fold increase compared to the HIV-negative controls. Duodenal macromolecule permeability was partially temperature-dependent and associated with epithelial apoptosis without altered expression of the analyzed tight junction proteins. In T84 monolayers, apoptosis induction increased, and both apoptosis and endocytosis inhibitors reduced macromolecule permeability. Using quantitative analysis, we demonstrate the increased macromolecule permeability of the intestinal mucosa in untreated HIV-infected patients. Combining structural and mechanistic studies, we identified two pathways of increased macromolecule translocation in HIV infection: transcytosis and passage through apoptotic leaks.<\/jats:p>","DOI":"10.3390\/cells12141887","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:47:38Z","timestamp":1689727658000},"page":"1887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Macromolecule Translocation across the Intestinal Mucosa of HIV-Infected Patients by Transcytosis and through Apoptotic Leaks"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1293-2484","authenticated-orcid":false,"given":"Susanne M.","family":"Krug","sequence":"first","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolin","family":"Gr\u00fcnhagen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Rheumatology and Infectious Diseases, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Allers","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Rheumatology and Infectious Diseases, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Bojarski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Rheumatology and Infectious Diseases, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1444-8976","authenticated-orcid":false,"given":"Joachim","family":"Seybold","sequence":"additional","affiliation":[{"name":"Antibiotic Stewardship Team, Medical Directorate, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Rheumatology and Infectious Diseases, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9947-5521","authenticated-orcid":false,"given":"J\u00f6rg-Dieter","family":"Schulzke","sequence":"additional","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 12203 Berlin, Germany"},{"name":"Department of Gastroenterology, Rheumatology and Infectious Diseases, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-J\u00f6rg","family":"Epple","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Rheumatology and Infectious Diseases, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"},{"name":"Antibiotic Stewardship Team, Medical Directorate, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ancuta, P., Kamat, A., Kunstman, K.J., Kim, E.Y., Autissier, P., Wurcel, A., Zaman, T., Stone, D., Mefford, M., and Morgello, S. 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