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

• Published in: Frontiers in immunology 2020-10, Vol.11, p.559635-559635
• Main Authors: Snyder, Lindsay M, Arora, Juhi, Kennett, Mary J, Weaver, Veronika, Cantorna, Margherita T
• Format: Article
• Language: English
• Subjects: Animals; barrier; Biomarkers; Citrobacter rodentium; Colitis - etiology; Colitis - metabolism; Colitis - mortality; Colitis - pathology; Dextran Sulfate - adverse effects; Disease Models, Animal; Disease Susceptibility; Enterobacteriaceae Infections - etiology; Enterobacteriaceae Infections - metabolism; Enterobacteriaceae Infections - mortality; Enterobacteriaceae Infections - pathology; gastrointestinal tract; Immunology; infection; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Mice; Mice, Knockout; Prognosis; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - metabolism; retinoic acid receptor; Retinoids - metabolism; Severity of Illness Index; Signal Transduction; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; vitamin A deficiency
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.559635

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, 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 dnRAR mice, with the exception of the T cell receptor (TCR)αβ+/CD8αα cells, which were significantly lower than in wildtype littermates. Challenging the dnRAR mice with dextran sodium sulfate to induce colitis or infection resulted in similar disease to wildtype littermates. Feeding mice vitamin A deficient diets reduced vitamin A status and the A- dnRAR mice developed more severe colitis and infection. In particular, retinoid signaling in the IEC was crucial for the A- host to survive early infection following . 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- dnRAR mice was ineffective for preventing lethality following 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.