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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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| 格式: | Dissertation |
| 语言: | 英语 |
| 出版: |
Philipps-Universität Marburg
2017
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| 总结: | 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. |
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| DOI: | 10.17192/z2017.0293 |