Gut microbiota mediates clearance of C. rodentium by phagocytes

Infections with enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli (E. coli) are a major cause of diarrhoea in the developing world. Asymptomatic EPEC-carriers are thought to be an important reservoir for these pathogens since they excrete pathogens unknowingly and thereby infe...

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1. Verfasser: Zarzycka, Agnieszka Ewa
Beteiligte: Steinhoff, Ulrich (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2017
Medizin
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Zusammenfassung:Infections with enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli (E. coli) are a major cause of diarrhoea in the developing world. Asymptomatic EPEC-carriers are thought to be an important reservoir for these pathogens since they excrete pathogens unknowingly and thereby infect other people and spread disease. With C. rodentium we were able to mimic long-termcarrier situations in mice without gut microbiota. This enabled us to investigate how commensal bacteria initiate clearance of enteropathogens. During this work, we could show that a healthy gut microbiota influences the expression of inflammatory factors like IL-17A and consequently CXCL2 and ICAM- 1, thus mediating migration of neutrophils into the colon. Furthermore, we found that commensal bacteria enhance the phagocytic activity of neutrophils and in parallel elevate colonic IgG levels, subsequently leading to an efficient uptake and killing of C. rodentium. However, our findings demonstrate that in absence of gut microbiota these immune responses are impaired. As a consequence, this leads to a lifelong persistence of C. rodentium, which adapt a commensal-like phenotype at late time points of infection. Importantly, we here show that impaired immune responses can be restored by the transfer of gut microbiota, thus enabling clearance of the enteropathogen. Although many prior investigations have focused on infection with C. rodentium, it was not understood how gut microbiota induces clearance of the enteropathogen. The findings from this work might provide information for microbiota mediated preventive and therapeutic treatments of asymptomatic EPEC-carriers.
DOI:http://dx.doi.org/10.17192/z2017.0293