TY  - JOUR
A1  - Däullary, Thomas
A1  - Imdahl, Fabian
A1  - Dietrich, Oliver
A1  - Hepp, Laura
A1  - Krammer, Tobias
A1  - Fey, Christina
A1  - Neuhaus, Winfried
A1  - Metzger, Marco
A1  - Vogel, Jörg
A1  - Westermann, Alexander J.
A1  - Saliba, Antoine-Emmanuel
A1  - Zdzieblo, Daniela
T1  - A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection
JF  - Gut Microbes
N2  - Infection research largely relies on classical cell culture or mouse models. Despite having delivered invaluable insights into host-pathogen interactions, both have limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models in vitro. Here, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an in vitro model of the human small intestinal epithelium exhibiting in vivo-like characteristics. Using the foodborne pathogen Salmonella enterica serovar Typhimurium, we demonstrated the applicability of our model to enteric infection research in the human context. Infection assays coupled to spatio-temporal readouts recapitulated the established key steps of epithelial infection by this pathogen in our model. Besides, we detected the upregulation of olfactomedin 4 in infected cells, a hitherto unrecognized aspect of the host response to Salmonella infection. Together, this primary human small intestinal tissue model fills the gap between simplistic cell culture and animal models of infection, and shall prove valuable in uncovering human-specific features of host-pathogen interplay.
KW  - intestinal enteroids
KW  - biological scaffold
KW  - Salmonella Typhimurium
KW  - OLFM4
KW  - NOTCH
KW  - filamentous Salmonella Typhimurium
KW  - bacterial migration
KW  - bacterial virulence
KW  - 3D tissue model
KW  - olfactomedin 4
KW  - infection
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350451
VL  - 15
IS  - 1
ER  - 
TY  - JOUR
A1  - Trujillo‐Viera, Jonathan
A1  - El‐Merahbi, Rabih
A1  - Schmidt, Vanessa
A1  - Karwen, Till
A1  - Loza‐Valdes, Angel
A1  - Strohmeyer, Akim
A1  - Reuter, Saskia
A1  - Noh, Minhee
A1  - Wit, Magdalena
A1  - Hawro, Izabela
A1  - Mocek, Sabine
A1  - Fey, Christina
A1  - Mayer, Alexander E.
A1  - Löffler, Mona C.
A1  - Wilhelmi, Ilka
A1  - Metzger, Marco
A1  - Ishikawa, Eri
A1  - Yamasaki, Sho
A1  - Rau, Monika
A1  - Geier, Andreas
A1  - Hankir, Mohammed
A1  - Seyfried, Florian
A1  - Klingenspor, Martin
A1  - Sumara, Grzegorz
T1  - Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
JF  - EMBO Molecular Medicine
N2  - Lipids are the most energy‐dense components of the diet, and their overconsumption promotes obesity and diabetes. Dietary fat content has been linked to the lipid processing activity by the intestine and its overall capacity to absorb triglycerides (TG). However, the signaling cascades driving intestinal lipid absorption in response to elevated dietary fat are largely unknown. Here, we describe an unexpected role of the protein kinase D2 (PKD2) in lipid homeostasis. We demonstrate that PKD2 activity promotes chylomicron‐mediated TG transfer in enterocytes. PKD2 increases chylomicron size to enhance the TG secretion on the basolateral side of the mouse and human enterocytes, which is associated with decreased abundance of APOA4. PKD2 activation in intestine also correlates positively with circulating TG in obese human patients. Importantly, deletion, inactivation, or inhibition of PKD2 ameliorates high‐fat diet‐induced obesity and diabetes and improves gut microbiota profile in mice. Taken together, our findings suggest that PKD2 represents a key signaling node promoting dietary fat absorption and may serve as an attractive target for the treatment of obesity.
KW  - chylomicron
KW  - fat absorption
KW  - intestine
KW  - obesity
KW  - protein kinase D2/PKD2/PRKD2
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239018
VL  - 13
IS  - 5
ER  -