Sara Lindén research group
The mucosal tissues of the gastrointestinal, respiratory, reproductive and urinary tracts and the surface of the eye present an enormous surface area to the exterior environment. Mucosal tissues represent the site of infection or a route of access for the majority of bacteria that cause human diseases. To protect the epithelial cells, the mucosal surfaces are covered by a layer of secreted mucins that have a decoy/cleaning function, and underneath the mucus layer the cell-surface mucins are a dominant feature of the apical surface of mucosal epithelial cells. The cell surface mucins provide a barrier and signalling function and are involved in tumour metastasis as well as regulation of cell proliferation. In infection, precancerous lesions and cancer, the expression and spatial distribution of mucins change. Each mucin carries around 100 different oligosaccharide structures, and some of these change rapidly in response to infection in a way that alters the bacterial adhesion targets. Thus, the mucin barrier is dynamic and responsive and is likely to play a major role during infection and malignant transformation.
H. pylori (green) interacting with the membrane bound mucin MUC1 (red). Nuclei are stained blue.
We investigate the role of mucins during host defense against bacteria, as well as the biological function of changes in mucosal mucin expression and glycosylation associated with disease. Currently it is not known whether these changes are beneficial for the host or the pathogen, or if they take part in malignant processes or merely accompany them, and furthering the knowledge in this area may lead to novel ways of treating disease.
The main host-pathogen systems being investigated are: Helicobacter pylori infection and gastric cancer development. H. pylori chronically infects half of the World’s population and is the main aetiological agent causing duodenal ulcers, gastric ulcers, gastric adenocarcinoma and mucosal associated lymphoid tissue (MALT) lymphoma. Gastric cancer is globally the second most prevalent cause of death due to malignancy.
Campylobacter jejuni, enteropathogenic Escherichia coli and enterohaemorrhagic E. coli infection of the intestine. These pathogens are considered to be the major cause of diarrhoeal disease in both the developed and developing world. In the US C. jejuni infection costs up to US $6.2 billion annually, while in the developing world most of the 2-3 million childhood-deaths from diarrhoeal disease which occur each year are caused by these bacteria. Like H. pylori, C. jejuni infection can have long term sequelae including intestinal MALT lymphoma and the debilitating autoimmune disease Guillain-Barre Syndrome.