TY  - JOUR
A1  - Eder, Sascha
A1  - Hollmann, Claudia
A1  - Mandasari, Putri
A1  - Wittmann, Pia
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Fink, Julian
A1  - Seibel, Jürgen
A1  - Schneider-Schaulies, Jürgen
A1  - Stigloher, Christian
A1  - Beyersdorf, Niklas
A1  - Dembski, Sofia
T1  - Synthesis and characterization of ceramide-containing liposomes as membrane models for different T cell subpopulations
JF  - Journal of Functional Biomaterials
N2  - A fine balance of regulatory (T\(_{reg}\)) and conventional CD4\(^+\) T cells (T\(_{conv}\)) is required to prevent harmful immune responses, while at the same time ensuring the development of protective immunity against pathogens. As for many cellular processes, sphingolipid metabolism also crucially modulates the T\(_{reg}\)/T\(_{conv}\) balance. However, our understanding of how sphingolipid metabolism is involved in T cell biology is still evolving and a better characterization of the tools at hand is required to advance the field. Therefore, we established a reductionist liposomal membrane model system to imitate the plasma membrane of mouse T\(_{reg}\) and T\(_{conv}\) with regards to their ceramide content. We found that the capacity of membranes to incorporate externally added azide-functionalized ceramide positively correlated with the ceramide content of the liposomes. Moreover, we studied the impact of the different liposomal preparations on primary mouse splenocytes in vitro. The addition of liposomes to resting, but not activated, splenocytes maintained viability with liposomes containing high amounts of C\(_{16}\)-ceramide being most efficient. Our data thus suggest that differences in ceramide post-incorporation into T\(_{reg}\) and T\(_{conv}\) reflect differences in the ceramide content of cellular membranes.
KW  - liposome
KW  - ceramide
KW  - cell membrane model
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286130
SN  - 2079-4983
VL  - 13
IS  - 3
ER  - 
TY  - JOUR
A1  - Derakhshani, Shaghayegh
A1  - Kurz, Andreas
A1  - Japtok, Lukasz
A1  - Schumacher, Fabian
A1  - Pilgram, Lisa
A1  - Steinke, Maria
A1  - Kleuser, Burkhard
A1  - Sauer, Markus
A1  - Schneider-Schaulies, Sibylle
A1  - Avota, Elita
T1  - Measles virus infection fosters dendritic cell motility in a 3D environment to enhance transmission to target cells in the respiratory epithelium
JF  - Frontiers in Immunology
N2  - Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.
KW  - dendritic cell
KW  - cell migration
KW  - measles virus
KW  - 3D tissue model
KW  - sphingosine-1-phosphate
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201818
VL  - 10
IS  - 1294
ER  -