TY  - JOUR
A1  - Schwerk, Christian
A1  - Papandreou, Thalia
A1  - Schuhmann, Daniel
A1  - Nickol, Laura
A1  - Borkowski, Julia
A1  - Steinmann, Ulrike
A1  - Quednau, Natascha
A1  - Stump, Carolin
A1  - Weiss, Christel
A1  - Berger, Jürgen
A1  - Wolburg, Hartwig
A1  - Claus, Heike
A1  - Vogel, Ulrich
A1  - Ishikawa, Hiroshi
A1  - Tenenbaum, Tobias
A1  - Schroten, Horst
T1  - Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier
JF  - PLoS One
N2  - Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens.
KW  - gene expression
KW  - plexus epithelial-cells
KW  - central-nervous-system
KW  - microvascular endothelial-cells
KW  - choroid-plexus
KW  - in vitro
KW  - brain barrier
KW  - tight junctions
KW  - meningococcal disease
KW  - bacterial meningitis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131459
VL  - 7
IS  - 1
ER  - 
TY  - JOUR
A1  - Nono, Justin Komguep
A1  - Pletinckx, Katrien
A1  - Lutz, Manfred B.
A1  - Brehm, Klaus
T1  - Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro
JF  - PLoS Neglected Tropical Diseases
N2  - Background: Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC) are key effectors in shaping the immune response and among the first cells encountered by the parasite during an infection. Although it is assumed that E. multilocularis, by excretory/secretory (E/S)-products, specifically affects DC to deviate immune responses, little information is available on the molecular nature of respective E/S-products and their mode of action. Methodology/Principal Findings: We established cultivation systems for exposing DC to live material from early (oncosphere), chronic (metacestode) and late (protoscolex) infectious stages. When co-incubated with Echinococcus primary cells, representing the invading oncosphere, or metacestode vesicles, a significant proportion of DC underwent apoptosis and the surviving DC failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation markers and did not undergo apoptosis. After pre-incubation with primary cells and metacestode vesicles, DC showed a strongly impaired ability to be activated by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex E/S-products. While none of the larvae induced the secretion of pro-inflammatory IL-12p70, the production of immunosuppressive IL-10 was elevated in response to primary cell E/S-products. Finally, upon incubation with DC and naive T-cells, E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T cells in vitro. Conclusions: This is the first report on the induction of apoptosis in DC by cestode E/S-products. Our data indicate that the early infective stage of E. multilocularis is a strong inducer of tolerance in DC, which is most probably important for generating an immunosuppressive environment at an infection phase in which the parasite is highly vulnerable to host attacks. The induction of CD4+CD25+Foxp3+ T cells through metacestode E/S-products suggests that these cells fulfill an important role for parasite persistence during chronic echinococcosis.
KW  - granulosus
KW  - hydatid disease
KW  - metacestode vesicles
KW  - antigen-B
KW  - alveoar echinococcosis
KW  - TGF-BETA
KW  - regulatory T cells
KW  - gene expression
KW  - Brugia Malayi
KW  - TNF-alpha
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134280
VL  - 6
IS  - 2
ER  -