Abstract

In industrialized countries bacterial intestinal infections are commonly caused by enteropathogenic Enterobacteriaceae. The interaction of the microbiota with the host immune system determines the adequacy of an appropriate response against pathogens. In this study we addressed whether the probiotic Bifidobacterium adolescentis is protective during intestinal Yersinia enterocolitica infection. Female C57BL/6 mice were fed with B. adolescentis, infected with Yersinia enterocolitica, or B. adolescentis fed and subsequently infected with Yersinia enterocolitica. B. adolescentis fed and Yersinia infected mice were protected from Yersinia infection as indicated by a significantly reduced weight loss and splenic Yersinia load when compared to Yersinia infected mice. Moreover, protection from infection was associated with increased intestinal plasmacytoid dendritic cell and regulatory T-cell frequencies. Plasmacytoid dendritic cell function was investigated using depletion experiments by injecting B. adolescentis fed, Yersinia infected C57BL/6 mice with anti-mouse PDCA-1 antibody, to deplete plasmacytoid dendritic cells, or respective isotype control. The B. adolescentis-mediated protection from Yersinia dissemination to the spleen was abrogated after plasmacytoid dendritic cell depletion indicating a crucial function for pDC in control of intestinal Yersinia infection. We suggest that feeding of B. adolescentis modulates the intestinal immune system in terms of increased plasmacytoid dendritic cell and regulatory T-cell frequencies, which might account for the B. adolescentis-mediated protection from Yersinia enterocolitica infection.

Highlights

  • Infection with Yersinia enterocolitica e.g. by ingestion of contaminated food or drinking water can cause severe diarrhea, enterocolitis, and mesenteric lymphadenitis [1,2]

  • The Bifidobacterium adolescentis-Mediated Protection from Yersinia enterocolitica Infection is Associated with an Increased Proportion of PDCA-1-Positive pDCs

  • First we analyzed the effect of B. adolescentis feeding on the intestinal mucosal immune system, in particular on the composition of intraepithelial Dendritic cells (DCs) and the lamina propria DC subpopulations and the course of Yersinia enterocolitica infection

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Summary

Introduction

Infection with Yersinia enterocolitica e.g. by ingestion of contaminated food or drinking water can cause severe diarrhea, enterocolitis, and mesenteric lymphadenitis [1,2]. Several studies demonstrate that the host’s intestinal microbiota is crucial in defining the host’s susceptibility towards intestinal infections. This is demonstrated by the significant influence of antibiotic treatment on the composition of the intestinal microbiota, in both, human subjects [5,6,7,8] and mice [9,10] where increased susceptibility towards enteropathogenic bacteria was shown [11,12]. The secretion of Reg3c could be restored via stimulation of intestinal TLR4 thereby boosting the innate immune resistance of antibiotic-treated mice against infections with VRE [13]. Antibiotic-induced disruption of the intestinal microbiota enhances the susceptibility of human hosts to infections with nontyphoidal Salmonellae [14], and is a prerequisite for infection of mice with Salmonella typhimurium [15,16]

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