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Altered innate defenses in the neonatal gastrointestinal tract in response to colonization by neuropathogenic Escherichia coli

Birchenough, GM; Johansson, ME; Stabler, RA; Dalgakiran, F; Hansson, GC; Wren, BW; Luzio, JP; (2013) Altered innate defenses in the neonatal gastrointestinal tract in response to colonization by neuropathogenic Escherichia coli. Infection and Immunity , 81 (9) pp. 3264-3275. 10.1128/IAI.00268-13. Green open access

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Abstract

Two-day-old (P2), but not nine-day-old (P9), rat pups are susceptible to systemic infection following gastrointestinal colonization by Escherichia coli K1. Age dependency reflects the capacity of colonizing K1 to translocate from gastrointestinal (GI) tract to blood. A complex GI microbiota developed by P2, showed little variation over P2-P9 and did not prevent stable K1 colonization. Substantial developmental expression was observed over P2-P9, including up-regulation of genes encoding components of the small intestinal (α-defensins Defa24 and Defa-rs1) and colonic (trefoil factor Tff2) mucus barrier. K1 colonization modulated expression of these peptides: developmental expression of Tff2 was dysregulated in P2 tissues and was accompanied by a decrease in mucin Muc2. Conversely, α-defensin genes were up-regulated in P9 tissues. We propose that incomplete development of the mucus barrier during early neonatal life and the capacity of colonizing K1 to interfere with mucus barrier maturation provide opportunities for neuropathogen translocation into the bloodstream.

Type: Article
Title: Altered innate defenses in the neonatal gastrointestinal tract in response to colonization by neuropathogenic Escherichia coli
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/IAI.00268-13
Publisher version: http://dx.doi.org/10.1128/IAI.00268-13
Language: English
Additional information: Copyright © American Society for Microbiology, [Infection and Immunity, 81(9), 2013, 3264-3275, 10.1128/IAI.00268-1]
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/1398202
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