The zymogen granule membrane glycoprotein 2 (GP2) as trigger for host tropism and individuality of intestinal infections.

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The zymogen granule membrane glycoprotein 2 (GP2) is expressed by the follicle associated epithelium of the intestine, affects intestinal infections via binding of the bacterial adhesin FimH, might play a role in Crohns disease and is an immunomodulator of the innate as well as acquired immunity. In our previous work using Enterobacteriaceae we showed that binding to GP2 is specific for single bacterial species or pathotypes but also specific for host animal species.Based upon our comprehensive preliminary work we would like to clarify in detail mechanisms of this phenomenon by means of the following hypothesis: bacterial intestinal infections are often host specific and individual. GP2 and its interactions with bacteria on the one hand and effects via intestinal epithelial cells to cells of the intestinal immune system on the other hand are basics for host tropism and individuality.In our preliminary work we used only one out of four described human GP2 isoforms. Since GP2 of other mammal species is unknown yet, we will define other mammal GP2 including possible isoforms. GP2 and GP2 isoforms are compared to each other. For identification of new GP2 we screen published DNA sequences for sequences homologue to GP2 or use tissues of pigs or cattle to generate cDNA. Identified GP2 types and isoforms are recombinantly expressed. We perform binding studies in a screening format using GP2 proteins and 400 well defined bacterial isolates. In parallel, we transduce cell lines to express each GP2 isoform in its host specific background. These cells are used for adhesion and invasion studies. In addition, cell lines of phagocytes are incubated with fluorescence labelled bacteria (phagocytosis assays). Finally, we perform first in vitro infection studies to show whether recombinant GP2 can inhibit bacterial infections.