All Projects

Funding: Ministry of Science and Culture of Lower Saxony, 186.057 EUR

Project Details:
The worldwide occurrence of resistant bacteria limits the efficiency of antibiotic-based treatment concepts. Therefore, new promising therapeutic approaches are needed, such as the strengthening of the host's defense by stimulating the immune system. Since the complex host-pathogen interactions are still poorly understood, detailed knowledge is required to apply therapeutic strategies based on the innate immune system. However, animal-free in vitro model systems for infection and interaction studies as well as for drug screenings are only a real alternative if the results obtained can be reliably transferred to the in vivo situation. However, due to lack of complexity, incorrect cell differentiation status, and lack of physiological conditions, in vitro systems do not sufficiently accurately simulate the in vivo situation during infection or inflammatory response.
The project aims to characterize the innate immune response with focus on lung epithelial cells against respiratory bacteria such as the human pathogen Staphylococcus aureus or the zoonotic pathogen Streptococcus suis in vitro and ex vivo. The complexity of the infection model is significantly increased by physiologically relevant oxygen conditions (defined hypoxic conditions, <10% O2 by means of a hypoxia glove box) and by 3D co-cultivation of human and porcine pulmonary epithelial cells and neutrophils.
This study will help to minimize false negative results in screening potential protective immunomodulators or antibiotics that are found to be effective in vitro but ineffective in vivo. Increased complexity of the model system also allows the in vitro system to approach the in vivo situation and will help to reduce the number of animals.

Results:

Influence of Oxygen on Function and Cholesterol Composition of Murine Bone Marrow-Derived Neutrophils.

Branitzki-Heinemann K, Brogden G, von Köckritz-Blickwede M.

Methods Mol Biol. 2020;2087:223-233. doi: 10.1007/978-1-0716-0154-9_17.

 

Differentiation and Functionality of Bone Marrow-Derived Mast Cells Depend on Varying Physiologic Oxygen Conditions.

Möllerherm H, Meier K, Schmies K, Fuhrmann H, Naim HY, von Köckritz-Blickwede M, Branitzki-Heinemann K.

Front Immunol. 2017 Nov 30;8:1665. doi: 10.3389/fimmu.2017.01665. eCollection 2017.

Cooperation Partners:

Prof. A. Bleich, PhD - MHH, Institut für Versuchstierkunde

Prof. Dr. M. Stiesch - MHH, Klinik für Zahnärztliche Prothetik und Biomedizinische Werkstoffkunde

Prof. Dr. Gerhard Breves - TiHo, Physiologisches Institut

Prof. Dr. Pablo Steinberg - TiHo, Institut für Lebensmitteltoxikologie und Chemische Analytik

Prof. Dr. med. Tim Sparwasser - Dr. Luciana Berod

Twincore, Zentrum für Experimentelle und Klinische Infektionsforschung GmbH, Institut für Infektionsimmunologie,

Dr. Jörn Tongers - MHH, Klinik für Kardiologie und Angiologie

Prof. Dr. Jürgen Wienands, Dr. Niklas Engels -

Universitätsmedizin Göttingen, Institut für Zelluläre & Molekulare Immunologie

Prof. A. Bleich, PhD - MHH, Institut für Versuchstierkunde

Prof. Dr. Tobias Cantz - MHH, Exzellenzcluster REBIRTH, Klinik für Gas-troenterologie, Hepatologie und Endokrinologie

Dr. Tanja Hansen- Fraunhofer ITEM, Klinische Chemie und ADME

Dr. Andres Hilfiker - MHH, Klinik für Herz, Thorax-, Transplantations- und Gefäßchirurgie, LEBAO

Prof. Dr. Ulrich Martin, Dr. Ruth Olmer

MHH, Klinik für Herz, Thorax-, Transplantations- und Gefäßchirurgie, LEBAO

Prof. Dr. Axel Schambach, PhD, Dr. Michael Rothe - MHH, Institut für Experimentelle Hämatologie

Prof. Dr. Wolfgang Baumgartner - TiHo, Institut für Pathologie

Prof. Dr. Albert Osterhaus - TiHo, Research Center for Emerging Infections and Zoonoses (RIZ)

Prof. Dr. M. von Köckritz-Blickwede - TiHo, Research Center for Emerging Infections and Zoonoses (RIZ)/Institut für Physiologische Chemie

Prof. Dr. Dr. Daniel Strech - MHH, Institut für Geschichte, Ethik und Philosophie der Medizin

Prof. Dr. Nils Hoppe - Leibniz Universität Hannover, Leibniz Forschungsinitiative CELLS: Centre for Ethics and Law in the Life Sciences (CELLS-LUH)

Prof. A. Bleich, PhD - MHH, Institut für Versuchstierkunde

Project Details:
S. aureus is a multifaceted commensal organism and a potentially harmful human pathogen. It can cause a broad spectrum of infections, which can involve any organ. Beside toxin mediated diseases, it can also play a role as an intracellular pathogen. In vivo studies concern the association of S. aureus and gastrointestinal disorders focussed on the colonization of the gastrointestinal tract by S. aureus, and on the influence of staphylococcal toxins. In this study the influence of S. aureus infections on the function of human intestinal cells were investigated in an in vitro colon carcinoma (Caco)-2 cell model. It could be shown that S. aureus Newman wild type (WT) and the mutant strain S. aureus Newman Äeap exhibiting a lack of the extracellular adherence protein (Eap), were able to invade day 7 post-confluent Caco-2 cells followed by intracellular survival, persistence and replication, even though substantial less S. aureus Newman Äeap bacteria were invasive. Staphylococcal infection did not induce any cytotoxic effect observed by a membrane integrity test showing lactate-dehydrogenase (LDH)-release of infected cells remained unchanged compared to uninfected cells. This was in addition visualized microscopically with LIVE/DEAD Viability/Cytotoxicity Kit for mammalian cells after infection with S. aureus Newman WT expressing the green fluorescence protein (GFP). However, the function of the infected cells was altered: a decrease in enriched specific activity of sucrose from the marker glycoprotein human sucrase-isomaltase (hSI) was observable in the apical membrane fraction 48h after infection. Specific SI-activity was increased in the basolateral membrane fraction as well as decreased in the apical membrane fraction with no alterations in the catalytic capacity. Results obtained from this study suggest that infections with S. aureus could influence the sorting of hSI, leading to intestinal disorders followed by symptoms like diarrhea. Further investigations based on these results will give new insights in S. aureus gut infections and the association with gastrointestinal diseases, which could possibly enable therapeutic steps because of shedding light on the causes of symptoms.

Funding: DAAD Dres. Jutta & Georg Bruns Stiftung , 70.000 EUR

Project Details:
In Sudan, traditional medicinal plants continue to form the basis of rural medical care. This is due to the fact, that these medicines are easily available and cheap. In Sudanese folk medicine, some plants were claimed to have therapeutic values as for example Gum Arabic.
Gum Arabic is a dried exudate obtained from the branches and stems of Acacia senegal and closely related species. It is a complex polysaccharide of high molecular weight which contains neutral sugars as rhamnose, arabinose, and galactose; acids such as glucuronic acid; minerals such as calcium, magnesium, potassium, sodium, and phosphorous. In folk medicine, Gum Arabic has been reported to be used for the treatment of inflammation of the intestinal mucosa, and to cover inflamed surfaces.
A study conducted in Sudan has proven that the addition of Gum Arabic to rat’s diet has positive effect in lowering serum cholesterol and triacylglycerol (TAG) levels. Interestingly, drugs that are able to interfere with cholesterol synthesis as statins have been shown by us to induce antimicrobial activity of neutrophils against S. aureus, namely the formation of neutrophil extracellular traps (NETs). Thus, it may be hypothesized that medicinal plant extracts as Gum Arabic might have a protective effect on S. aureus infections by boosting antimicrobial neutrophil functions and thereby improve the outcome of an infection.
Since there is nothing known about the potential of Gum Arabic extracts to boost the host immune system, the goal of this study is to test Gum Arabic extracts for their ability to enhance the antimicrobial capabilities of phagocytes such as neutrophils as the first line of defense against invading pathogens.

Results:

Baien SH, Seele J, Henneck T, Freibrodt C, Szura G, Moubasher H, Nau R, Brogden G, Mörgelin M, Singh M, Kietzmann M, von Köckritz-Blickwede M, de Buhr N. 2020. Antimicrobial and Immunomodulatory Effect of Gum Arabic on Human and Bovine Granulocytes Against Staphylococcus aureus and Escherichia coli. Front Immunol 10:1-18.

 

Baien SH, Langer MN, Heppelmann M, von Köckritz-Blickwede M, de Buhr N. 2018. Comparison Between K3EDTA and Lithium Heparin as Anticoagulant to Isolate Bovine Granulocytes From Blood. Front Immunol 9:1-13.

Cooperation Partners:

Dr. Jana Seele und Prof. Roland Nau: Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Göttingen,

Germany und Department of Neuropathology, University Medical Center Göttingen, Georg-August-University Göttingen, Göttingen, Germany

Funding: LUH, 30.000 EUR

Project Details:
An efficient, cost-effective test system will be established to test a large number of people as quickly as possible
(> 1,000/day). In three process steps i) Samples are taken in mobile test centers
(Throat swab according to the standard of the Robert Koch Institute), ii) processed (RNA isolation) and iii) evaluated by means of PCR analysis according to the Charité Berlin1 protocol. Positive results from the screening will be
diagnostically confirmed by certified laboratories and reported to the local health department. The mobile stations
are built on the basis of flexibly set up shipping containers and both for taking swabs
as well as the purification set up. In this way, a strict separation between the removal and
the processing of potentially infectious material in the mobile container and the subsequent analysis of the
non-infectious RNA samples secured in separate laboratories.

Funding: Bundeswehr, 60.690 EUR

Project Details:
Da sich die COVID-19-Pandemie weiter ausbreitet, ist die frühzeitige Identifizierung von SARS-CoV-2-infizierten Personen von entscheidender Bedeutung für die Unterbrechung der Infektionsketten. Flüchtige organische Verbindungen, die bei Infektionen der Atemwege entstehen, können bestimmte Geruchsabdrücke verursachen, die von trainierten Hunden mit hoher Präzision erkannt werden können.

Results:

Medical scent detection dogs can discriminate samples from SARS-CoV-2 infected individuals from controls. Performance of dogs is comparable between sweat, urine and saliva samples.

https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05281-3

Cooperation Partners:

Bundeswehr

Funding: BmBF, 331.351 EUR

Project Details:
Entwicklung und Evaluation eines auf Dengue-Virus zugeschnittenen Systems für Immunogenitätsstudien