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Viral-bacterial interactions in co-infections of the respiratory tract of pigs

Methods:

Use of porcine precision-cut lung slices (PCLS) and primary porcine airway epithelial cells differentiated under air-liquid interphase conditions (ALI cultures) to study host-pathogen interactions during mono- and coinfections of respiratory cells in vitro.


Project description:

Co-Infections in the respiratory tract play an important role in modern intensive production systems of agricultural animals. In respiratory infections of swine viral-bacterial co-infections by porcine influenza virus (SIV) and Streptococcus suis (S. suis) represent an important paradigm for multifactorial infectious diseases of animals.  Though this is known for many years, our understanding of the molecular interactions between pathogens and the host is very sketchy. It is very difficult to study this in experimental infections and, therefore, it is important to develop suitable in vitro models which mimic as closely as possible the in vivo situation.
In the present project we further clarify the molecular interactions between SIV, S. suis and the host in co-infections of the primary target cells, i.e. differentiated porcine respiratory epithelial cells. For this, we use two porcine ex vivo models previously established in our laboratory, precision-cut lung slices (PCLS) and air-liquid-interphase (ALI) cultures. Of the different possible effects in co-infections we focus on direct effects of SIV on S. suis infections. This is based on our preliminary studies which revealed beneficial effects of SIV on S. suis. These effects were shown to involve two different processes occurring at different time points during infection. Initially, SIV promoted adherence of S. suis in a capsule-dependent manner. At a later stage we observed SIV-induced damage of ciliated epithelial cells leading to increased colonisation and invasion of S. suis which was shown to be independent of bacterial encapsulation. Currently we are elucidating the molecular mechanisms of both processes. We concentrate, on one hand, on the interactions between the sialic acid of the bacterial capsule with the viral haemagglutinin. Secondly, we analyze in particular the role of the cytolytic toxin suilysin in SIV-promoted colonisation and invasion of S. suis.

 

Funding:

DFG

 

Project Lead:

Prof. Dr. Peter Valentin-Weigand (peter.valentin@tiho-hannover.de; 0511-953-7362)

Institute for Microbiology, University of Veterinary Medicine Hannover, Foundation, Germany

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