AUTHOR=Snyder Lindsay M. , Arora Juhi , Kennett Mary J. , Weaver Veronika , Cantorna Margherita T. 

TITLE=Retinoid Signaling in Intestinal Epithelial Cells Is Essential for Early Survival From Gastrointestinal Infection

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.559635

DOI=10.3389/fimmu.2020.559635

ISSN=1664-3224

ABSTRACT=<p>Vitamin A deficiency (A–) increases morbidity and mortality to gastrointestinal (GI) infection. Blocking retinoid signaling (dominant negative retinoic acid receptor, dnRAR) in intestinal epithelial cells (IEC, <sup>IEC</sup>dnRAR) had no effect on vitamin A absorption, the expression of tight junction proteins or the integrity of the barrier. Immune cells in the gut were present in normal frequencies in the <sup>IEC</sup>dnRAR mice, with the exception of the T cell receptor (TCR)αβ+/CD8αα cells, which were significantly lower than in wildtype littermates. Challenging the <sup>IEC</sup>dnRAR mice with dextran sodium sulfate to induce colitis or <italic>Citrobacter rodentium</italic> infection resulted in similar disease to wildtype littermates. Feeding mice vitamin A deficient diets reduced vitamin A status and the A– <sup>IEC</sup>dnRAR mice developed more severe colitis and <italic>C. rodentium</italic> infection. In particular, retinoid signaling in the IEC was crucial for the A– host to survive early infection following <italic>C. rodentium</italic>. Treating A– mice with retinoic acid (RA) beginning on the day of infection protects most mice from early lethality. However, RA treatment of the A– <sup>IEC</sup>dnRAR mice was ineffective for preventing lethality following <italic>C. rodentium</italic> infection. Retionid signaling in IEC is critical, especially when there are reduced levels of dietary vitamin A. IEC are direct targets of vitamin A for mounting early defense against infection.</p>