Is alpha-dystroglycan the missing link in the mechanism of enterocyte uptake and translocation of Mycobacterium avium paratuberculosis?
Mycobacterium avium paratuberculosis (MAP) is an important animal pathogen with a potential role in human disease. MAP is recognized to cause severe diarrheas and wasting syndrome in patients infected by the human immuno-deficiency virus. Recently, there is also growing evidence that MAP is somehow involved into the patho-mechanisms of Crohn's disease. However, the mechanism how MAP binds to the intestinal mucosa and consecutively invades and translocates the intestinal epithelial cells is still unknown. Here it is suggested, that MAP enters the intestinal cells via the dystrophin-glycoprotein-complex (DGC) in a similar manner as known from Mycobacterium tuberculosis in peripheral Schwann cell invasion. Recent approaches to identify the mechanism of intestinal MAP uptake revealed several molecules which are therefore thought to be involved in MAP cell invasion. Nevertheless, there is no comprehensive connection so far to link all identified mechanisms together. Since the DGC has a direct association to all identified molecules and mechanisms and therefore seems to be the missing link, it is hypothesized now, that MAP binds to alpha-dystroglycan and exploits an endogenous recycling mechanism to control the dystroglycan expression levels to enter and translocate the intestinal cells. Since there are options to modify dystroglycan this might be a potential new target to prevent or even treat intestinal MAP infections.
Warth
Arne
A
Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany. arne.warth@med.uni-heidelberg.de <arne.warth@med.uni-heidelberg.de>
D000818:Animals; D003424:Crohn Disease / Q000209:etiology / Q000382:microbiology; D003599:Cytoskeleton / Q000378:metabolism; D049030:Dystroglycans / Q000502:physiology*; D020895:Enterocytes / Q000382:microbiology* / Q000502:physiology*; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D016927:Mycobacterium avium subsp. paratuberculosis / Q000472:pathogenicity*; D010283:Paratuberculosis / Q000209:etiology* / Q000382:microbiology / Q000503:physiopathology; D020741:rho GTP-Binding Proteins / Q000235:genetics
D006001:Glycoconjugates; D016023:Integrins; D049030:Dystroglycans; D020741:rho GTP-Binding Proteins