TY - JOUR
T1 - Retinoic acid mediated clearance of Citrobacter rodentium in vitamin A deficient mice requires CD11b+ and T cells
AU - Snyder, Lindsay M.
AU - McDaniel, Kaitlin L.
AU - Tian, Yuan
AU - Wei, Cheng Hsin
AU - Kennett, Mary J.
AU - Patterson, Andrew D.
AU - Catharine Ross, A.
AU - Cantorna, Margherita T.
N1 - Funding Information:
This work was supported by the National Institutes of Health (R01AT005378) and the United State Department of Agriculture (2914-38420-21822). We thank Dr. Randolph J. Noelle, Dartmouth, Lebanon, NH for kindly providing the dnRAR-α fl/fl mice. We also thank Veronika Weaver for her diligent work managing the mouse colony and aiding in tissue processing.
Funding Information:
This work was supported by the National Institutes of Health (R01AT005378) and the United State Department of Agriculture (2914-38420-21822).
Publisher Copyright:
© 2007 - 2019 Frontiers Media S.A. All Rights Reserved.
PY - 2019
Y1 - 2019
N2 - Vitamin A deficiency affects over 250 million preschool-age children worldwide and is associated with increased childhood mortality and risk of developing enteric infections. Vitamin A deficient (A–) mice developed chronic Citrobacter rodentium infection. A single oral dose of retinoic acid (RA) at d7 post-infection was sufficient to induce clearance of the pathogen in A– mice. RA treatment of A– mice induced il17 expression in the colon. In A– mice, colonic IL-17 was primarily produced by CD11b+ cells; however, in A+ mice, the major source of colonic IL-17 was CD4+ T cells. To determine the cellular targets of vitamin A required for host resistance to C. rodentium, mice that express a dominant negative (dn) retinoic acid receptor (RAR) in T cells (T-dnRAR) or macrophage/neutrophils (LysM-dnRAR) were used. T-dnRAR mice had T cells that produced a robust intestinal IL-17 response and for 40% of the mice was enough to clear the infection. The remainder of the T-dnRAR mice developed a chronic infection. A–LysM-dnRAR mice developed early lethal infections with surviving mice becoming chronically infected. RA treatment of A– LysM-dnRAR mice was ineffective for inducing colonic IL-17 or clearing C. rodentium. Retinoid signaling is required in T cells and CD11b+ cells for complete elimination of enteric pathogens.
AB - Vitamin A deficiency affects over 250 million preschool-age children worldwide and is associated with increased childhood mortality and risk of developing enteric infections. Vitamin A deficient (A–) mice developed chronic Citrobacter rodentium infection. A single oral dose of retinoic acid (RA) at d7 post-infection was sufficient to induce clearance of the pathogen in A– mice. RA treatment of A– mice induced il17 expression in the colon. In A– mice, colonic IL-17 was primarily produced by CD11b+ cells; however, in A+ mice, the major source of colonic IL-17 was CD4+ T cells. To determine the cellular targets of vitamin A required for host resistance to C. rodentium, mice that express a dominant negative (dn) retinoic acid receptor (RAR) in T cells (T-dnRAR) or macrophage/neutrophils (LysM-dnRAR) were used. T-dnRAR mice had T cells that produced a robust intestinal IL-17 response and for 40% of the mice was enough to clear the infection. The remainder of the T-dnRAR mice developed a chronic infection. A–LysM-dnRAR mice developed early lethal infections with surviving mice becoming chronically infected. RA treatment of A– LysM-dnRAR mice was ineffective for inducing colonic IL-17 or clearing C. rodentium. Retinoid signaling is required in T cells and CD11b+ cells for complete elimination of enteric pathogens.
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U2 - 10.3389/fimmu.2018.03090
DO - 10.3389/fimmu.2018.03090
M3 - Article
C2 - 30671060
AN - SCOPUS:85060367402
SN - 1664-3224
VL - 10
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - JAN
M1 - 3090
ER -