TY - JOUR
T1 - Retinoic acid amplifies the host immune response to LPS through increased T lymphocytes number and LPS binding protein expression
AU - Seguin-Devaux, Carole
AU - Hanriot, Didier
AU - Dailloux, Michèle
AU - Latger-Cannard, Véronique
AU - Zannad, Faiez
AU - Mertes, Paul Michel
AU - Longrois, Dan
AU - Devaux, Yvan
N1 - Funding Information:
C. Seguin-Devaux and Y. Devaux were supported by grants from the Association de Recherche et d’Information Scientifique en Cardiologie and the Association des Infirmiers et Médecins Anesthésistes-Réanimateurs.
PY - 2005/12/21
Y1 - 2005/12/21
N2 - Vitamin A deficiency is associated with increased susceptibility to infection but the effects of Vitamin A supplementation on host response to pathogens are controversial. This study investigated the mechanisms by which all-trans retinoic acid (atRA) modulates the host immune response in an experimental model of Vitamin A supplementation before and after challenge with LPS in rats. We show here that a supplementation with five daily injections of 10 mg/kg atRA increased the number of T lymphocytes in the peripheral blood. In addition, we show that atRA increased the expression of the LPS binding protein (LBP), a component of the LPS recognition system. The retinoic acid receptor (RAR)α agonist Ro 4060-55 but not the pan-retinoid X receptors (RXRs) agonist Ro 2573-86 mimicked the effects of atRA on LBP expression suggesting that atRA enhances LBP expression through a RARα-mediated pathway. In order to investigate the significance of increased LBP expression we challenged atRA-supplemented rats with the Gram-positive bacteria Listeria monocytogenes (LM) that activates the immune response independently from LBP. In sharp contrast to our previous observations that atRA supplementation enhances IFN-γ expression and NOS2 pathway activation in LPS-challenged rats [Devaux, Y., Grosjean, S., Seguin, C., David, C., Dousset, B., Zannad, F., Meistelman, C., de Talancé, N., Mertes, P.M., Ungureanu-Longrois, D., 2000. Retinoic acid and host-pathogen interactions: effects on inducible nitric oxide synthase in vivo. Am. J. Physiol. 279, E1045-E1053], atRA did not increase the LM-induced IFN-γ expression and NOS2 pathway activation. Overall, these data demonstrate that although atRA induces a "priming" of the immune system characterized by increased T lymphocytes number and LBP expression, the profile of the immune response depends on the inflammatory/infectious stimulus. These results could explain why Vitamin A supplementation could have beneficial/neutral or deleterious effects according to the identity of the infectious pathogen.
AB - Vitamin A deficiency is associated with increased susceptibility to infection but the effects of Vitamin A supplementation on host response to pathogens are controversial. This study investigated the mechanisms by which all-trans retinoic acid (atRA) modulates the host immune response in an experimental model of Vitamin A supplementation before and after challenge with LPS in rats. We show here that a supplementation with five daily injections of 10 mg/kg atRA increased the number of T lymphocytes in the peripheral blood. In addition, we show that atRA increased the expression of the LPS binding protein (LBP), a component of the LPS recognition system. The retinoic acid receptor (RAR)α agonist Ro 4060-55 but not the pan-retinoid X receptors (RXRs) agonist Ro 2573-86 mimicked the effects of atRA on LBP expression suggesting that atRA enhances LBP expression through a RARα-mediated pathway. In order to investigate the significance of increased LBP expression we challenged atRA-supplemented rats with the Gram-positive bacteria Listeria monocytogenes (LM) that activates the immune response independently from LBP. In sharp contrast to our previous observations that atRA supplementation enhances IFN-γ expression and NOS2 pathway activation in LPS-challenged rats [Devaux, Y., Grosjean, S., Seguin, C., David, C., Dousset, B., Zannad, F., Meistelman, C., de Talancé, N., Mertes, P.M., Ungureanu-Longrois, D., 2000. Retinoic acid and host-pathogen interactions: effects on inducible nitric oxide synthase in vivo. Am. J. Physiol. 279, E1045-E1053], atRA did not increase the LM-induced IFN-γ expression and NOS2 pathway activation. Overall, these data demonstrate that although atRA induces a "priming" of the immune system characterized by increased T lymphocytes number and LBP expression, the profile of the immune response depends on the inflammatory/infectious stimulus. These results could explain why Vitamin A supplementation could have beneficial/neutral or deleterious effects according to the identity of the infectious pathogen.
KW - LPS binding protein
KW - Lipopolysaccharide
KW - Listeria monocytogenes
KW - T cells
KW - Vitamin A
UR - http://www.scopus.com/inward/record.url?scp=30044444381&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/16309824
U2 - 10.1016/j.mce.2005.10.006
DO - 10.1016/j.mce.2005.10.006
M3 - Article
C2 - 16309824
AN - SCOPUS:30044444381
SN - 0303-7207
VL - 245
SP - 67
EP - 76
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -