publications of the research group of immune control (IMMK)http://hdl.handle.net/10033/6205992024-03-29T10:08:08Z2024-03-29T10:08:08ZLongitudinal proliferation mapping in vivo reveals NADPH oxidase-mediated dampening of Staphylococcus aureus growth rates within neutrophils.Seiß, Elena AKrone, AnnaFormaglio, PaulineGoldmann, OliverEngelmann, SusanneSchraven, BurkhartMedina, EvaMüller, Andreas Jhttp://hdl.handle.net/10033/6218062019-08-30T11:28:19Z2019-04-05T00:00:00ZLongitudinal proliferation mapping in vivo reveals NADPH oxidase-mediated dampening of Staphylococcus aureus growth rates within neutrophils.
Seiß, Elena A; Krone, Anna; Formaglio, Pauline; Goldmann, Oliver; Engelmann, Susanne; Schraven, Burkhart; Medina, Eva; Müller, Andreas J
Upon the onset of inflammatory responses, bacterial pathogens are confronted with altered tissue microenvironments which can critically impact on their metabolic activity and growth. Changes in these parameters have however remained difficult to analyze over time, which would be critical to dissect the interplay between the host immune response and pathogen physiology. Here, we established an in vivo biosensor for measuring the growth rates of Staphylococcus aureus (S. aureus) on a single cell-level over days in an ongoing cutaneous infection. Using intravital 2-photon imaging and quantitative fluorescence microscopy, we show that upon neutrophil recruitment to the infection site and bacterial uptake, non-lethal dampening of S. aureus proliferation occurred. This inhibition was supported by NADPH oxidase activity. Therefore, reactive oxygen production contributes to pathogen containment within neutrophils not only by killing S. aureus, but also by restricting the growth rate of the bacterium.
2019-04-05T00:00:00ZFilamin A Phosphorylation at Serine 2152 by the Serine/Threonine Kinase Ndr2 Controls TCR-Induced LFA-1 Activation in T Cells.Waldt, NatalieSeifert, AnkeDemiray, Yunus EmreDevroe, EricTurk, Benjamin EReichardt, PeterMix, CharlieReinhold, AnnegretFreund, ChristianMüller, Andreas JSchraven, BurkhartStork, OliverKliche, Stefaniehttp://hdl.handle.net/10033/6217722019-08-30T11:24:25Z2018-01-01T00:00:00ZFilamin A Phosphorylation at Serine 2152 by the Serine/Threonine Kinase Ndr2 Controls TCR-Induced LFA-1 Activation in T Cells.
Waldt, Natalie; Seifert, Anke; Demiray, Yunus Emre; Devroe, Eric; Turk, Benjamin E; Reichardt, Peter; Mix, Charlie; Reinhold, Annegret; Freund, Christian; Müller, Andreas J; Schraven, Burkhart; Stork, Oliver; Kliche, Stefanie
The integrin LFA-1 (CD11a/CD18) plays a critical role in the interaction of T cells with antigen presenting cells (APCs) to promote lymphocyte differentiation and proliferation. This integrin can be present either in a closed or in an open active conformation and its activation upon T-cell receptor (TCR) stimulation is a critical step to allow interaction with APCs. In this study we demonstrate that the serine/threonine kinase Ndr2 is critically involved in the initiation of TCR-mediated LFA-1 activation (open conformation) in T cells. Ndr2 itself becomes activated upon TCR stimulation and phosphorylates the intracellular integrin binding partner Filamin A (FLNa) at serine 2152. This phosphorylation promotes the dissociation of FLNa from LFA-1, allowing for a subsequent association of Talin and Kindlin-3 which both stabilize the open conformation of LFA-1. Our data suggest that Ndr2 activation is a crucial step to initiate TCR-mediated LFA-1 activation in T cells.
2018-01-01T00:00:00ZCharacterization of mice with a platelet-specific deletion of the adapter molecule ADAP.Rudolph, Jochen MichaelGuttek, KarinaWeitz, GabrieleMeinke, Clara AntoniaKliche, StefanieReinhold, DirkSchraven, BurkhartReinhold, Annegrethttp://hdl.handle.net/10033/6217382019-08-30T11:30:26Z2019-03-04T00:00:00ZCharacterization of mice with a platelet-specific deletion of the adapter molecule ADAP.
Rudolph, Jochen Michael; Guttek, Karina; Weitz, Gabriele; Meinke, Clara Antonia; Kliche, Stefanie; Reinhold, Dirk; Schraven, Burkhart; Reinhold, Annegret
The adhesion and degranulation-promoting adapter protein (ADAP) is expressed in T cells, NK cells, myeloid cells, and platelets. The involvement of ADAP in the regulation of receptor-mediated inside-out signaling leading to integrin activation is well characterized, especially in T cells and in platelets. Due to the fact that animal studies using conventional knock-out mice are limited by the overlapping effects of the different ADAP-expressing cells, we generated conditional ADAP knock-out mice (ADAPfl/fl PF4-Cretg). We observed that loss of ADAP restricted to the megakaryocytic lineage has no impact on other hematopoietic cells even after stimulation conditions. ADAPfl/fl PF4-Cretg mice showed thrombocytopenia in combination with reduced plasma levels of PF4 and TGF-β1. In vitro, platelets from these mice revealed reduced P-selectin expression, lower TGF-β1 release, diminished integrin αIIbβ3 activation and decreased fibrinogen binding after stimulation with podoplanin, the ligand of the C-type lectin-like receptor-2 (CLEC-2). Furthermore, loss of ADAP was associated with impaired CLEC-2-mediated activation of PLCγ2 and Erk1/2. Induction of experimental autoimmune encephalomyelitis (EAE) in mice lacking ADAP expression in platelets caused a more severe disease. In vivo administration of TGF-β1 early after T cell transfer improved EAE severity in mice with loss of ADAP restricted to platelets. Our results reveal a regulatory function of ADAP in platelets in vitro and during autoimmune disease EAE in vivo.
2019-03-04T00:00:00ZMemantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of K1.3 potassium channels, AKT and ERK1/2 signaling.Lowinus, TheresaHeidel, Florian HBose, TanimaNimmagadda, Subbaiah CharySchnöder, TinaCammann, ClemensSchmitz, IngoSeifert, UlrikeFischer, ThomasSchraven, BurkhartBommhardt, Ursulahttp://hdl.handle.net/10033/6216902019-08-30T11:32:39Z2019-01-16T00:00:00ZMemantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of K1.3 potassium channels, AKT and ERK1/2 signaling.
Lowinus, Theresa; Heidel, Florian H; Bose, Tanima; Nimmagadda, Subbaiah Chary; Schnöder, Tina; Cammann, Clemens; Schmitz, Ingo; Seifert, Ulrike; Fischer, Thomas; Schraven, Burkhart; Bommhardt, Ursula
Treatment of acute leukemia is challenging and long-lasting remissions are difficult to induce. Innovative therapy approaches aim to complement standard chemotherapy to improve drug efficacy and decrease toxicity. Promising new therapeutic targets in cancer therapy include voltage-gated K We analyzed acute lymphoid (Jurkat, CEM) and myeloid (HL-60, Molm-13, OCI-AML-3) leukemia cell lines and patients' acute leukemic blasts after treatment with either drug alone or the combination of cytarabine and memantine. Patch-clamp analysis was performed to evaluate inhibition of K Our study demonstrates that memantine inhibits K Our study underlines inhibition of K
2019-01-16T00:00:00Z