Retinoic acid amplifies the host immune response to LPS through increased T lymphocytes number and LPS binding protein expression

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• 作者：Carole Seguin-Devaux ; Didier Hanriot ; Michè ; le Dailloux ; Vé ; ronique Latger-Cannard ; Faiez Zannad ; Paul-Michel Mertes ; Dan Longrois and Yvan Devaux
• 关键词：Vitamin A ; Lipopolysaccharide ; Listeria monocytogenes ; T cells ; LPS binding protein
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2005
• 出版时间：21 December 2005
• 年：2005
• 卷：245
• 期：1-2
• 页码：67-76
• 全文大小：473 K

文摘

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.