Publikationsserver der Universitätsbibliothek Marburg

Titel:Gut microbiota mediates clearance of C. rodentium by phagocytes
Autor:Zarzycka, Agnieszka Ewa
Weitere Beteiligte: Steinhoff, Ulrich (Prof. Dr.)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0293
URN: urn:nbn:de:hebis:04-z2017-02935
DOI: https://doi.org/10.17192/z2017.0293
DDC: Medizin, Gesundheit
Titel(trans.):Die Darmmikrobiota induziert die Eliminierung von C. rodentium durch Phagozyten
Publikationsdatum:2017-05-03
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
Phagozytose, C. rodentium, phagocytosis, C. rodentium, C. rodentium, Neutrophil, Neutrophil, neutrophil, Phagozytose

Summary:
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.

Zusammenfassung:
Infektiöse Durchfallerkrankungen, wie die durch enterohämorrhagische (EHEC) und enteropathogene (EPEC) E. coli verursachten, stellen besonders in Entwicklungsländern ein großes medizinisches Problem dar. Symptomlose Langzeitträger werden als gefährliches Reservoir angesehen, weil sie die Infektion unwissentlich verbreiten. Mit C. rodentium, einem Modelkeim für EHEC/EPEC Infektionen in der Maus, konnten wir in keimfreien Mäusen eine Langzeitinfektion etablieren, um den Einfluss kommensaler Bakterien für die Abwehr von enteropathogenen Keimen zu erforschen. Es konnte gezeigt werden, dass die normale, intestinale Mikrobiota die Expression inflammatorischer Faktoren wie IL-17A, CXCL2 und ICAM-1 beeinflusst, die an der Migration von Neutrophilen in das Colon beteiligt sind. Zusätzlich konnten wir zeigen, dass kommensale Keime die phagozytische Aktivität von Neutrophilen und die Konzentration an IgG im Colon erhöhen und somit eine effiziente Aufnahme und Abtötung von C. rodentium ermöglichen. Wir konnten weiterhin zeigen, dass diese Immunreaktionen in Abwesenheit von Darmbakterien stark beeinträchtigt sind, sodass C. rodentium lebenslang in keimfreien Mäusen persistiert und sich vom pathogenen in ein kommensales Bakterium verwandelt. Von enormer Bedeutung ist der Befund, dass die antibakterielle Abwehr durch den Transfer von Darmbakterien wiederhergestellt werden kann und es zu einer Eliminierung der enteropathogenen Keime kommt. Obwohl Infektionen mit C. rodentium im Fokus vieler früherer Forschungsarbeiten standen, war bisher noch unverstanden, wie Darmbakterien eine Eliminierung der enteropathogenen Bakterien induzieren. Die aus dieser Arbeit gewonnen Erkenntnisse können für die präventive und therapeutische Behandlung asymptomatischer EPEC- Langzeitträger von Bedeutung sein.

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