Research

Funding: Boehringer Ingelheim Vetmedica GmbH, 16.666 EUR

Project Details:
Zeitgleiche Isolierung und Charakterisierung von S. suis und PRRSV aus Organsystemen sezierter Schweine. Charakterisierung der Effizienz der Immunausweichmechanismen von S. suis Isolaten.

Project Details:
Respiratory multifactorial diseases cause problems in swine populations worldwide. Pathogens as porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae (M. hyopneumoniae)may be involved in disease development in combination with management, husbandry, and environmental factors. In a conventional farm, where piglets were not vaccinated against PCV2, it will be examined to what extent the introduction of vaccination against PCV2 has an effect on animal health. In addition the effect of the used combinaory vaccine (PCV2+M.hyopneumoniae) will be evaluated in comparison to simultaneously administered mono- vaccines against PCV2 and M. hyopneumoniae.
In a two-phase trial, 524 (phase 1) or 521 (phase 2) clinically healthy piglets are included at the first week of life. In the first phase, performance parameters will be compared in animals vaccinated against M. hyopneumoniae only (group A) or vaccinated against PCV2 and M. hyopneumoniae (group B). In phase 2, vaccinations against PCV2 and M. hyopneumoniae with different vaccines are compared (groups C and D). Performance parameters recorded will include total losses, daily weight gains during suckling, rearing, and fattening, and pathogen loads in serum (PCV2) or tracheobronchial secretions (M. hyopneumoniae). In addition, lungs are assessed at slaughter.

Funding: Deutsche Forschungsgemeinschaft (DFG), 199.450 EUR

Project Details:
Der Respirationstrakt ist eine häufige Eintrittspforte für Krankheitserreger. Das Hundestaupevirus (CDV) sowie das nahverwandte Masernvirus müssen die Barriere des Atemwegsepithels überwinden, um zu ihren Zielzellen, den Immunzellen, zu gelangen. Nectin-4, der einzige bekannte Rezeptor für beide Viren auf Epithelzellen, ist ein basolaterales Protein. Nach Aufnahme werden die Morbilliviren von polarisierten Zellen des respiratorischen Epithels über die apikale Membran freigesetzt, gelangen in die Luftwege und können so den Wirt verlassen. Es ist bislang nicht bekannt wie das CDV im Anfangsstadium der Infektion die Barriere des Atemwegsepithels überwindet und in den Wirt eindringt. In dem geplanten Projekt soll daher mittels Präzisionslungenschnitten und Air-liquid-interface-Kulturen differenzierter respiratorischer Zellen analysiert werden, wie CDV das respiratorische Epithel überwindet und subepitheliale Zielzellen infiziert. Hierbei werden die infizierten Zelltypen, der Infektionsverlauf, zytopathogene Effekte und die Regeneration des Epithels in beiden Kultursystemen näher charakterisiert. Der Einsatz von CDV-Mutanten, die Defekte in der Rezeptorerkennung aufweisen (SLAM-blinde und Epithelzell-Rezeptor-blinde CDV), ermöglicht hierbei gezielte Aussagen über das Spektrum der infizierbaren Zellen und die Effizienz der Infektion. Als zweite Möglichkeit des Überwindens der Epithelbarriere wird untersucht, ob CDV über die parazelluläre Route eindringen kann. Außerdem wird der Einfluss verschiedener Umweltfaktoren, von denen bekannt ist, dass sie die Verbindung zwischen Epithelzellen (tight junctions) öffnen, auf den Infektionsverlauf ermittelt. Zusätzlich soll geklärt werden, ob infizierte Makrophagen oder dendritische Zellen bei der Überwindung der Epithelzellbarriere als Vektoren fungieren und so bei der Ausbreitung der Infektion behilflich sind. In weiteren in vitro-Experimenten wird mittels Zytokinexpressionsanalysen bestimmt, welche Auswirkung die CDV-Infektion auf immunologische Funktionen in der Lunge hat. Im Rahmen der CDV-Infektion des Atemwegepithels soll außerdem der Einfluss einer Co-Infektion (Bordetella bronchiseptica) untersucht werden. Das Projekt wird entscheidend für das Verständnis der Pathogenese der CDV-Infektion beitragen. Es wird auch hilfreich sein für das Verständnis anderer Viren, die den Respirationstrakt als Durchgangsstation benutzen, um in ihren Wirt einzudringen.

Funding: BMBF, 1.351.062 EUR

Project Details:
Zoonotic flaviviruses, such as TBEV and JEV, can infect a number of different vertebrate hosts, but cause clinical disease only in some species while others remain unaffected. Moreover, many flaviviruses that are pathogenic in humans cause clinical symptoms in only a small fraction of infected individuals, of which only a portion will go on to develop severe complications, such as encephalitis, hemorrhagic disease or auto-immune disorders. The determinants of these dramatically different disease outcomes between host species and individuals from the same species are currently not well understood. Molecular mechanisms at the cellular level could play a role in the observed differences between susceptible host species. Advanced techniques, such as mRNA-Seq, real-time RT-PCR, and surface plasmon resonance will be applied for the comparative analysis of virus-host interactions at molecular and cellular levels in different host species to identify host-dependent factors that restrict or facilitate flavivirus infection.
Virus-specific antibodies play a major role in the protection from infection by neutralization of infectious viral particles or mediation of immune effector functions. However, virus-specific antibodies can also lead to the enhancement of flavivirus infections, especially in the case of secondary infections, and antibody-induced immune effector functions can contribute to the often observed immunopathogenesis in viral infections. Second-generation serological assays and functional immune effector studies can be used to measure individual antibody profiles against the complete viral proteome. Antibody profiles may vary between asymptomatic and symptomatic individuals and across different host species, and can contribute to the identification of biomarkers and predictors of disease outcome.

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:
Das Brain natriuretic Peptide (BNP), auch als b-Typ natriuretisches Peptid bezeichnet, ist ein Hormon, das in der Herzmuskulatur gebildet und bei Dehnung der Herzkammern ins Blut abgegeben wird. Dieses Hormon besitzt wichtige Aufgaben in der Herz-Kreislaufregulation und wird in der Human- und Kleintiermedizin zur Diagnostik von Herzerkrankungen verwendet.
Das Vorkommen dieses Hormonones im Herzen von Papageien soll untersucht und eine Verwendung in der Diagnostik von Herzerkrankungen dieser Voegelarten überprüft werden.

Results:

https://www.mdpi.com/2306-7381/9/2/64

Project Details:
Untersuchungen zur Verbesserung der kulturellen Re-Isolierung des Erregers Mycoplasma hyopneumoniae aus Lungengewebeproben des Schweins mittels polyklonaler Antikörper und Verifizierung der Modifikationen in einem standardisierten Infektionsmodell.

Funding: Niedersächsische Tierseuchenkasse, Hannover, 72.750 EUR

Project Details:
Vereinzelt wurden im Blut von Milchkühen aus Betrieben Niedersachsens Hemoplasmen (Mykoplasma wenyonii, Cand Mykoplasma hemobos) sowie Hepaciviren nachgewiesen. Bislang sind Prävalenz, Bedeutung für die Milchviehgesundheitheit und Übertragungswege von Hemoplasmen nicht hinreichend bekannt. Auch sind die Übertragungswege von Hepaciviren nicht untersucht. Ziel der Studie ist daher die Prävalenz von Hemoplasmen und deren Bedeutung für die Gesundheit von Milchkühen abzuschätzen. Ferner soll geprüft werden, ob bei infizierten Tieren intrauterine Übertragungen von Hepaciviren und Hemoplasmen auf die Nachkommen vorkommen.

Cooperation Partners:

Dr. Bernd Hoffmann, Institut für Virusdiagnostik, Friedrich Loeffler Institut, Insel Riems

Dr. Mark Holsteg, Rindergesundheitsdienst Nordrhein-Westalen, Bad Sassendorf

Prof. Dr. Wolfgang Hölzle,Fakultät Agrarwissenschaften der Universität Hohenheim, Infektions- und Umwelthygiene bei Nutztieren, Stuttgart/Hohenheim

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, 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