Dr. B. Linz

Research areas

Pathogenesis of Bordetella pertussis infection

Bordetella pertussis is the causative agent of Whooping Cough, a notifiable respiratory disease. Although the current acellular vaccines protect against the disease symptoms, there is growing evidence that B. pertussis continues to circulate in even highly vaccinated populations. The recent pertussis epidemics in many countries, including Germany, have shown how remarkably little we know and understand the pathophysiology during the initial colonization of the human upper airways by B. pertussis. This initial, catarrhal phase of B. pertussis infection, which is highly contagious, is characterized by massive mucus secretion, a heavily runny nose, sneezing and mild coughing, spreading copious amounts of bacteria. Detailed investigation of this catarrhal phase is necessary for the development of new therapeutics and improved pertussis vaccines that prevent transmission of the pathogen, but progress has been hampered by the lack of suitable experimental systems.

In my laboratory, we apply our novel and innovative experimental mouse models that enable us, for the first time, to study the catarrhal phase of B. pertussis infection in mechanistic detail. To identify the bacterial factors that elicit it we analyze the gene expression profile of B. pertussis during this phase. Using isogenic knock-out or loss-of-function mutants in comparison to the parental wild type bacteria, we assess the role of these factors during the initial colonization, during inflammation of the host mucosa, mucus production, bacterial shedding from the nose of infected mice, and during transmission between cage mates. We analyze the interaction of the bacterial factors with host cell receptors and the effect on the host immune response.

These studies are complemented by in vitro analyses at the air-liquid interface cell culture. In this system, bronchial cells differentiate into a pseudostratified epithelium that forms functional tight and adherens junctions as well as cilia. Following our hypothesis that these bacterial factors damage the functional integrity of the epithelium, we determine their effect on the epithelial layer by measuring the trans-epithelial electrical resistance, bacterial transmigration through the cell layer, and by examining the structural integrity of the cell layer by confocal microscopic using fluorescent antibodies against various cell junction proteins.

 

Publications

 

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