ESF-GS ABINEP / Teilprojekt M3.P5
Elucidating the roles of secretory immunoglobulins in asthma under homeostatic and infectious conditions
Asthma is estimated to affect more than 330 million people worldwide and acute disease exacerbations are a major cause of morbidity and hospitalization in asthmatic individuals. Streptococcus pneumoniae is a frequent colonizer of the human nasopharynx and the pre-dominant bacterial pathogen detected in the upper airways of exacerbating asthma in patients. Case-control studies identified asthma as a risk factor for severe pneumococcal disease.
The secretory immunoglobulins (SIgs), secretory IgA (SIgA) and secretory IgM (SIgM), as well as their exclusive epithelial transport molecule, the polymeric immunoglobulin receptor (pIgR), are critical elements of respiratory mucosal host defense - deficiencies are associated with an increased susceptibility to bacterial infections in mice and humans. In this context, it was shown that chronic respiratory disease is intimately linked to differential pIgR-expression, and thus altered airway mucosal SIg-transport in mice and humans.
While the vital contributions of pIgR and SIgs for mucosal antimicrobial defense as well the crosstalk with the intestinal microbiota are well known, there is currently no true consensus about the roles of these molecules in asthma, asthma exacerbations and microbiota composition in the lung, respectively. IL-4, a hallmark cytokine in asthmatic disease, is known to be a potent inducer of epithelial pIgR-expression and SIg-transport and increased airway SIgA levels were reported in asthma patients. In this regard, SIgA has been assigned immunoregulatory functions such as prevention of airway hyperresponsiveness and eosinophilic infiltration as well as pro-inflammatory effects e.g. eosinophil degranulation and superoxide production. In frame of the proposed project we aim to elucidate the implications of airway SIgs for asthmatic individuals under homeostatic and infectious conditions.
Dr. med. Nadine Waldburg (niedergelassene Pneumologin, Magdeburg)
Dr. Sabine Stegemann-Koniszewski, Universitätsklinik für Pneumologie, Magdeburg (http://pneumologie.ovgu.de/Forschung.html)