@masterthesis{Hartmann, type = {Bachelor Thesis}, author = {Hartmann, S{\"o}ren}, title = {Regulation of dendritic migration in response to BCG}, url = {http://nbn-resolving.de/urn:nbn:de:hbz:1383-opus4-4969}, school = {Hochschule Rhein-Waal}, pages = {50}, abstract = {As tuberculosis is still the number one leading cause of death in humans due to a single infectious agent, prevention of infection is a key tactic in fighting it. Even though the vaccine BCG exists for tuberculosis since the beginning of the 20thcen-tury, it lacks efficacy and does not provide sustainable protection. An important step to develop a long-term immunity is the expansion of antigen-specific T cells in the lymph node. For T-cell priming to occur, the pathogen and/or its antigen has to be transported from the site of infection to the T-cell zone of the draining lymph node. This step is done by migratory Dendritic cells (DCs). DCs reside as sentinels in tis-sue, where after pathogen encounter, internalize the pathogen, process its antigens and migrate to the draining lymph node. Using a modified protocol, developed by Bollampali et al. (2015), during a previous study done Dr. Rothfuchs team, we investigated the mechanisms involved in the migration of DCs after injection of BCG. For this we injected mice with different inhibitors and recep-tor antagonists. It is worth mentioning that in a yet unpublished previous work we in-hibited the enzymes COX-1 and COX-2 systemically, using indomethacin, and showed a decreased number of DCs migrating to the draining popliteal lymph node after BCG in-jection compared to mice not injected with the inhibitor. Following our experiment, we decided to investigate the receptors of one of the down-stream products of COX, PGE2 and the corresponding receptors EP2 and EP4. Based on other studies two of the four receptors of PGE2, EP2 and EP4, are important for the mi-gration of DCs. We then injected mice with antagonists for these two either separate or simultaneously. Even though their affinities and the sustainability of the reaction caus-ing PGE2signalling are different, both receptors were able to compensate for each other, but a decreased number of DCs were found in the lymph node when both antagonists were injected. This and the results of the COX inhibition suggest a role for PGE2 on DC migration. Based on these results we decided to look at MMP-9, a molecule regulated by PGE2 sig-nalling. However, inhibition of MMP-9 in our model did not impact on DC migration. It is unclear if treatment with the MMP-9 inhibitor used failed or if MMP-9 is indeed not important in BCG-triggered DC migration. In conclusion in this thesis we show a role for EP2 and EP4 on DC migration after BCG injection but failed to show the same for MMP-9.}, language = {de} }