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Prebiotic Oligosaccharides Potentiate Host Protective Responses against L. Monocytogenes Infection

Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA
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Pathogens 2017, 6(4), 68; https://doi.org/10.3390/pathogens6040068
Received: 12 October 2017 / Revised: 5 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
(This article belongs to the Special Issue Listeria monocytogenes and Its Interactions with the Host)
Prebiotic oligosaccharides are used to modulate enteric pathogens and reduce pathogen shedding. The interactions with prebiotics that alter Listeria monocytogenes infection are not yet clearly delineated. L. monocytogenes cellular invasion requires a concerted manipulation of host epithelial cell membrane receptors to initiate internalization and infection often via receptor glycosylation. Bacterial interactions with host glycans are intimately involved in modulating cellular responses through signaling cascades at the membrane and in intracellular compartments. Characterizing the mechanisms underpinning these modulations is essential for predictive use of dietary prebiotics to diminish pathogen association. We demonstrated that human milk oligosaccharide (HMO) pretreatment of colonic epithelial cells (Caco-2) led to a 50% decrease in Listeria association, while Biomos pretreatment increased host association by 150%. L. monocytogenes-induced gene expression changes due to oligosaccharide pretreatment revealed global alterations in host signaling pathways that resulted in differential subcellular localization of L. monocytogenes during early infection. Ultimately, HMO pretreatment led to bacterial clearance in Caco-2 cells via induction of the unfolded protein response and eIF2 signaling, while Biomos pretreatment resulted in the induction of host autophagy and L. monocytogenes vacuolar escape earlier in the infection progression. This study demonstrates the capacity of prebiotic oligosaccharides to minimize infection through induction of host-intrinsic protective responses. View Full-Text
Keywords: prebiotic oligosaccharide; human milk oligosaccharide; eIF2 signaling; unfolded protein response; ER stress; autophagy; cell-mediated immunity (CMI); c-di-AMP prebiotic oligosaccharide; human milk oligosaccharide; eIF2 signaling; unfolded protein response; ER stress; autophagy; cell-mediated immunity (CMI); c-di-AMP
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Chen, P.; Reiter, T.; Huang, B.; Kong, N.; Weimer, B.C. Prebiotic Oligosaccharides Potentiate Host Protective Responses against L. Monocytogenes Infection. Pathogens 2017, 6, 68.

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