Research

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.

Project Details:
Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is one of the most important pathogens in pork production. In contrast to H. parasuis, which can also cause severe polyarthritis, polyserositis and meningitis, A. pleuropneumoniae is described as a lung pathogen leading to porcine pleuropneumonia. Nevertheless there are several case reports of arthritis, osteomyelitis, hepatitis or meningitis where A. pleuropneumoniae was the only detectable pathogen. Thus the aim of this study was do investigate the spreading of A. pleuropneumoniae to different body tissues during the acute phase of experimental aerosol infection as well as the influence of different sampling techniques on the detection rate.

Results:

https://link.springer.com/article/10.1186/s13567-018-0592-0

https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-018-1542-9

Project Details:
Die Pleuropneumonie des Schweines, verursacht durch Actinobacillus pleuropneumoniae, stellt eine sehr verlustreiche Infektionskrankheit der Schweine dar. Jüngste Untersuchungen zeigten, dass rassebedingt Unterschiede in der Empfänglichkeit der Schweine für diesen Infektionserreger existieren. Ziel dieser Untersuchungen ist das Verstehen von grundlegenden Mechanismen dieser reduzierten Empfänglichkeit durch das Aufdecken funktioneller Unterschiede in der angeborenen und erworbenen Immunität zwischen empfänglichen und resistenten Tieren.

Cooperation Partners:

Prof. Dr. Armin Saalmüller (Immunologie / VetmedUni Wien)

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: DAAD, 2.507 EUR

Project Details:
The bat genus Carollia, belonging to the family Phyllostomidae, is largely widespread in Central and South America and the species Carollia perspicillata, C. sowelli and C. castanea are known to occur sympatrically in some parts of these regions. These species are very similar in morphology and feeding habits. Moreover, they possess a polygynous social organization, with males defending roosting sites and attracting females in their harem.
It is suggested that vocalizations may play a fundamental role as premating isolation barrier in sympatrically living, cryptic species. This study aims at the comparison of the context-specific social call repertoires in the three Carollia species to evaluate their role as mechanism for maintaining species diversity. Especially, we hypothesize that vocalization from the courtship context differ more among species than those from e.g. agonistic interactions, and that bats are able to discriminate between sister species based on their vocalizations.

Results:

Bosia T., Villalobos F, and Schmidt S (2021) Evidence for vocal diversity during physical interference at the perch in sympatric Carollia species (Chiroptera: Phyllostomidae): a key to social organization and species coexistence? Zoological Journal of the Linnean Society. doi: 10.1093/zoolinnean/zlab040/6327516.

Cooperation Partners:

Prof. Federico Villalobos, Escuela de Ciencias Biológicas, Universidad Nacional de Costa Rica, Herediea, Costa Rica

Project Details:
In dem Konsortium werden die Genome der Familie Felidae aufgeklärt. Ziele sind die Verbesserung der Referenzgenomsequenz sowie die Charakterisierung der Diversität von Haus- und Wildkatzenarten.

Results:

Genova et al.,First genome-wide CNV mapping in FELIS CATUS using next generation sequencing data.BMC Genomics. 2018 Dec 10;19(1):895. doi: 10.1186/s12864-018-5297-2.

Cooperation Partners:

Tierkliniken

Zoos

Tiergärten

Project Details:
Harnsteine kommen bei Meerschweinchen häufig vor und stellen einen regelmäßigen Vorstellungsgrund für Meerschweinchen in der tierärztlichen Praxis dar. Harnsteine beim Meerschweinchen treten bei Meerschweinchen meistens in der Blase oder der Urethra bei weiblichen Tieren auf, seltener liegt eine Urolithiasis in den Ureteren vor. Über die Zusammensetzung von Harnsteinen aus unterschiedlichen Lokalisationen liegen beim Meerschweinchen noch keine Studien vor. Daher werden im Rahmen des Projekts Harnsteinanalysen von Meerschweinchen ausgewertet, die in Zusammenarbeit mit dem Harnsteinanalysezentrum Bonn analysiert wurden.

Cooperation Partners:

Kooperationspartner: Harnsteinanalysezentrum Bonn, Prof. Dr. Albrecht Hesse

Funding: DAAD, Konrad-Adenauer-Stiftung and external through collaboration

Project Details:
The proboscis monkey (Nasalis larvatus) is a large-bodied folivorous primate, forming harem and bachelor groups in lowland tropical rainforests in Borneo. Due to anthropogenic habitat loss and fragmentation, this primate species is highly endangered, and a better knowledge of their behavior and health status may improve their conservation and management. The goal of this project is to study its superficially known vocal signalling system and its intestinal parasite load to evaluate negative consequences of habitat fragmentation and the zoonotic risks that need to be considered when designing effective management programs. We investigate and compare those aspects in one-male (harem) and all-male (bachelor) groups in the Lower Kinabatangan Wildlife Sanctuary, Borneo, as well as in the Labuk Bay Sanctuary to study the role of vocalizations in governing spacing and cohesion. Furthermore, we assess intestinal parasite communities to link them to social grouping pattern and communication and to get insight into their significance for zoonotic diseases.

Results:

e.g.:

Scheumann, M., Röper, K. M., Nathan, S. K., & Goossens, B. (2022): Third-party vocal intervention in the proboscis monkey (Nasalis larvatus). Int. J. Primatol., 43: 1-14. https://doi.org/10.1007/s10764-021-00273-9

 

Klaus, A.; Strube, C.; Röper, K. M.; Radespiel, U.; Schaarschmidt, F.; Nathan, S.; Goossens, B.; Zimmermann, E.(2018): Fecal parasite risk in the endangered proboscis monkey is higher in an anthropogenically managed forest environment compared to a riparian rain forest in Sabah, Borneo in PlosOne 13(4). https:// doi.org/10.1371/journal.pone.0195584

 

Klaus, A.; Zimmermann, E.; Röper, K.M.; Radespiel, U.; Nathan, S.; Goossens, B.; Strube, C. (2017): Co-infection patterns of intestinal parasites in arboreal primates (proboscis monkeys, Nasalis larvatus)in Borneo.Int. Journ. for Parasitology: Parasites and Wildlife. 6(3): 320-329. https.//10.1016/j.ijppaw.2017.09.005

 

Röper, K.M.; Scheumann, M.; Wiechert, A.B.; Nathan, S.; Goossens, B.; Owren, M.J.; Zimmermann, E. (2014): Vocal acoustics in the endangered proboscis monkey (Nasalis larvatus). Am. J. Primatol. 76 (2): 192-201. https://doi.org/10.1002/ajp.22221

Cooperation Partners:

Dr. Benoit Goossens, Danau Girang Field Center, Malaysia, and Cardiff University, GB

Dr. Ikki Matsuda, Primate Research Center, Inumyama, Japan

Dipl. Biol. Kathrin M. Röper, Zoo Hannover

Project Details:
Funktionelle Kandidatengene, für die über Expressions- und Proteinanalysen beim Pferd oder bei anderen Tierarten und Mensch ein Einfluss auf die Befruchtungsrate nachgewiesen wurde, sollen als Kandidaten für die Fruchtbarkeit bei Hengsten und Stuten des Hannoverschen Warmbluts untersucht werden. Im Rahmen der Untersuchung sollen für diese Kandidatengene SNP-Marker mit signifikantem Einfluss auf die Reproduktionsleistung von Hengsten und Stuten entwickelt werden. Die Reproduktionsleistung der Pferde wird über die Trächtigkeitsrate pro Rosse und Decksaison erfasst. Dazu werden in Zusammenarbeit mit dem Niedersächsischen Landgestüt in Celle die Deckregister-Daten erhoben und ausgewertet. Die Auswertung erfolgt über Assoziationsanalysen für die Kandidatengene mit den Fruchtbarkeitsparametern.

Cooperation Partners:

Niedersächsisches Landgestüt Celle