DFG Research Training Group "TJ-Train" (GRK 2318/1)
Tight junctions and their proteins
Molecular features and actions in health and disease
Prof. Dr. Dr.
Med. Klinik für Gastroenterologie, Infektiologie & Rheumatologie,
Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin
Macromolecule uptake across the mucosa in HIV infection
Background Causing increased translocation of microbial components into the systemic circulation, a barrier defect of the gut epithelium is currently considered a key mechanisms of HIV
immunopathogenesis. However, despite its assumed prominent role for HIV pathogenesis, an epithelial barrier defect for microbial macromolecules has not been characterized in the intestinal mucosa
of HIV-infected individuals so far.
Aims Combining clinical data with functional, molecular and immunological analyses of mucosal samples obtained from HIV-infected patients and HIV-negative controls and with data obtained in
cell culture models, our project aims to characterize macromolecule translocation across the intestinal mucosa in HIV infection, define the route of macromolecule translocation, identify its
trigger mechanism and compare small and large intestinal mucosa in these respects.
Methods Methods employed will be: (i) Electrophysiological and transport physiological analysis of epithelial macromolecular transport and barrier function, (ii) immunofluorescence and
confocal microscopy, (iii) cell culture, (iv), quantification of epithelial protein expression and apoptosis by standard assays, (v) subset analysis of mucosal immune cells and quantification of
mucosal cytokine patterns by immunohistochemistry, flow cytometry, and cytometric bead array.
2nd cohort PhD doctoral student
1st cohort PhD doctoral student
1st cohort MD doctoral student
Participation with project
If a paper is not accessible, please mail to
Allers K, Puyskens A, Epple HJ, Schürmann D, Hofmann J, Moos V,
Schneider T (2016) The effect of timing of antiretroviral therapy on CD4+ T cell reconstitution in the intestine of HIV-infected patients.
Mucosal Immunology, 4th
edn. Mestecky J, Strober W, Kelsall B, Lambrecht B, Russell M, Cheroutre H (Eds.), Elsevier Academic Press, Burlington, San Diego, London
Epple HJ, Schneider T, Zeitz M (2015) Microbial translocation and the effects of HIV/SIV infection on mucosal
barrier function. In:
J. Acquir. Immune Defic. Syndr.
Allers K, Bösel D, Epple HJ, Karcher H, Schmidt W, Kunkel D, Geelhaar-Karsch A, Schinnerling K, Moos V, Schneider T
(2014) Effect of age on the CD4+ T cell impairment in HIV-infected persons without and with cART.
J. Infect. Dis.
Allers K, Fehr M, Conrad K, Epple HJ, Schürmann D, Geelhaar-Karsch A, Schinnerling K, Moos V, Schneider T
(2014) Macrophages accumulate in the gut mucosa of untreated HIV-infected patients.
Ann. N. Y. Acad. Sci.
Epple HJ, Zeitz M (2012) HIV infection and the intestinal mucosal barrier.
J. Virol. 84: 3259-3269
Allers K, Loddenkemper C, Hofmann J, Unbehaun A, Kunkel D, Moos V, Kaup FJ, Stahl-Hennig C, Epple HJ, Schneider T
(2010) Gut mucosal FOXP3+ regulatory CD4+ T cells and non-regulatory CD4+ T cells are differentially affected by SIV infection in rhesus macaques.
Epple HJ, Allers K, Troeger H, Kuhl A, Erben U, Fromm M, Zeitz M, Loddenkemper C, Schulzke JD, Schneider T
(2010) Acute HIV infection induces mucosal infiltration with CD4+ and CD8+ T cells, epithelial apoptosis, and a mucosal barrier defect.
Epple HJ, Schneider T, Troeger H, Kunkel D, Allers K, Moos V, Amasheh M, Loddenkemper C, Fromm M, Zeitz M,
Schulzke JD (2009) Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients.
Antimicrob. Agents Chemother.
Schulbin H, Bode H, Stocker H, Schmidt W, Zippel T, Loddenkemper C, Engelmann E, Epple HJ, Arastéh K, Zeitz M, Ullrich R
(2008) Cytokine expression in the colonic mucosa of HIV-infected individuals before and during nine months of antiretroviral therapy.
Epple HJ, Loddenkemper C, Kunkel D, Troeger H, Maul J, Moos V, Berg E, Ullrich R, Schulzke JD, Stein H, Duchmann R,
Zeitz M, Schneider T (2006) Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART.