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Current Projects

The role of neutrophil extracellular trap formation in equine recurrent uveitis (ERU)

Abstract 
The equine recurrent uveitis (ERU) is the main reason for blindness in horses, and 10% of the european horses are affected. Besides, ERU is an important available model for human autoimmune uveitis as the clinical and immune-pathological characteristics are quite similar (Deeg et al., 2002a). Various hypotheses are described in the literature that the putative initial trigger for the disease: On the one hand, infections with Leptospira interrogans are discussed as well as other bacterial, parasitic or viral infections. Independent of the initiating trigger, there are numerous indications that ERU is an immune-mediated disease based on an overwhelmed reaction of activated immune cells. Besides lymphocytes, also neutrophil granulocytes have been shown to be involved. Especially in the last years, there have been many descriptions of the role of neutrophil extracellular traps (NETs) in the context of autoimmune disease. For example, it was demonstrated that NETs are involved in the pathogenesis of systemic lupus erythematosus (SLE). Furthermore, NETs have been identified as a cause of keratoconjunctivitis sicca (dry eye disease (DED)) (Sonawane et al., 2012).
The research project presented here aims to provide essential insights into the role of NETs in the pathogenesis of ERU. It is based on own preliminary data from equine patient material, which lead to the hypothesis that ERU patients develop more NETs. In the current project, we will plan to examine NETs and NET markers in vitreous fluids, sera, and histological sections of the eye in samples from ERU-diseased horses compared to eye-healthy horses. Furthermore, a 3D-cell culture system will be established to mimic the external blood-retina barrier. With this system neutrophil transmigration studies will be conducted to characterize the activity of neutrophils and NET-formation at the blood-retina-barrier. These new findings on the role of neutrophils in ERU may help to develop knowledge for new treatment options against ERU.

 

Project leader

Nicole de Buhr, PhD and Prof.in Maren von Köckritz-Blickwede, Prof. Bernhard Ohnesorge

 

Contact person

Nicole de Buhr

 

Duration

01.01.2019 – 31.12.2021


Source/sponsor

DFG

Does an immune response triggered by Influenza-A-Virus induce growth factors for bacterial Co-Infection?

Abstract
Alone in Germany, over half a million people fall ill with pneumonia annually. Also in pig husbandry, respiratory infections lead to a burden of disease and high economic losses. Thereby, the occurrence of resistant pathogens poses new challenges for human and veterinary medicine. For developing new treatment strategies, understanding the host-pathogen interactions in complex co-infection models is fundamental.
Influenza-A-Virus (IAV) infections and bacterial co-infections are described as a combination for severe courses of illness in humans and pigs. The bacterial pathogens are often commensals of the upper respiratory tract and the tonsils. Frequently, the causes of bacterial lung infections with a severe acute course are unclear. In our preliminary work, we interestingly identified an unexpected phenotype for some human and porcine bacterial lung pathogens in connection with DNA NETs (neutrophil extracellular traps). This special defence mechanism of neutrophils is formed from extracellular DNA-structures of neutrophils and is originally described as an antimicrobial strategy against infectious agents. Our data demonstrate that NETs serve as a supplier for growth factors such as NAD and thereby improve the spread of NAD-dependent bacteria in the host. Therefore, the statement regarding the antimicrobial effect of NETs is challenged for some pathogens. This phenotype increases in strength when DNases are present, which digest the DNA-backbone of the NETs and therefore regulate the reduction in the NETs in the host. Since IAV can induce NETs, the host-pathogen interaction in co-infections of IAV and bacterial pathogens in humans and pigs should be investigated, focusing on the role of NETs. The core question is how far IAV-induced NETs-formation trigger the spread of bacterial co-infections.

 

Project leader

Nicole de Buhr, PhD


Duration

01.06.2020 – 31.05.2023


Source/sponsor

DLR (BMBF)

Evaluation of the clinical significance of co-infections with Streptococcus suis and the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) based on the characterization of involved field silicates

Co-infections with Streptococcus (S.) suis and PRRSV often cause serious diseases on pig farms. Synergistic effects of both pathogens were also confirmed under laboratory conditions. The aim of this study is to obtain isolates of both pathogens from diseased animals referred for diagnosis and to characterize them individually and in co-infection under in vitro conditions with different test methods according to their growth behaviour and their interaction with immune cells of the innate immune system.

 

 

Project leader

Nicole de Buhr, PhD

Prof.in Isabel Hennig Pauka

 

Contact person

Nicole de Buhr

 

Duration

August 2018 – Januar 2021

 

Source/sponsor

Boehringer Ingelheim Vetmedica GmbH

Kontakt
Dr. Tina Basler
Tel.:+49 511 953-6141
Fax.:+49 511 953-8675
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