Retinoic acid amplifies the host immune response to LPS through increased T lymphocytes number and LPS binding protein expression.
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 10mg/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)alpha 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 RARalpha-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-gamma 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-gamma 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.
Seguin-Devaux
Carole
C
Unité mixte UHP - INSERM U684, Faculté de Médecine, 9 avenue de la forêt de Haye, BP 184, Vandoeuvre-les-Nancy, Cedex, France.
Hanriot
Didier
D
Dailloux
Michèle
M
Latger-Cannard
Véronique
V
Zannad
Faiez
F
Mertes
Paul-Michel
PM
Longrois
Dan
D
Devaux
Yvan
Y
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001565:Benzoates / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007107:Immune System / Q000187:drug effects / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000907:Antibodies, Bacterial; D001565:Benzoates; D002352:Carrier Proteins; D007371:Interferon-gamma; D007376:Interleukin-2; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D052247:Nitric Oxide Synthase Type II; D018168:Receptors, Retinoic Acid; D013764:Tetrahydronaphthalenes; D014212:Tretinoin; D000099231:Lipopolysaccharide-Binding Protein; C068073:Am 580; C496318:Nos2 protein, rat