Elevated non-specific immunity and normal Listeria clearance in young and old vitamin D receptor knockout mice

Elevated non-specific immunity and normal Listeria clearance in young and old vitamin D receptor knockout mice
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DOI:
10.1093/intimm/dxn129
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发表时间:
2009-02-01
影响因子:
4.4
通讯作者:
Cantorna, Margherita T.
Cantorna, Margherita T.
中科院分区:
医学3区
文献类型:
--
作者:
Bruce, Danny;Whitcomb, James P.;Cantorna, Margherita T.

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1,25-二羟基维生素D-3 [1,25(OH)(2)D-3]和维生素D受体(VDR)是自身免疫的重要调节剂。VDR对小鼠抵抗原发性或继发性感染能力的影响尚未确定。年轻和年老的VDR敲除(KO)小鼠能够清除单核细胞增生李斯特菌的原发性和继发性感染。然而,在不存在VDR的情况下,清除动力学略有延迟。记忆性T细胞发育在年轻的VDR KO和野生型(WT)小鼠中没有差异;然而,老年VDR KO小鼠的记忆性T细胞显著少于其WT对应小鼠,但仍产生了足够的免疫应答,这是通过L.单核细胞增多症尽管在VDR KO小鼠中初级和次级免疫应答基本上是完整的,但与年老的WT小鼠相比,年老的VDR KO小鼠具有增加的细胞因子和抗体应答。特别是,年老的VDR KO小鼠具有升高的抗原非特异性抗体;然而,这些放大的免疫应答并不对应于更有效的李斯特菌清除。老龄VDR KO小鼠中抗体和细胞因子应答增加与这些小鼠对自身免疫的易感性增加一致。
1,25-Dihydroxyvitamin D-3 [1,25(OH)(2)D-3] and the vitamin D receptor (VDR) are important regulators of autoimmunity. The effect of the VDR on the ability of mice to fight a primary or secondary infection has not been determined. Young and old VDR knockout (KO) mice were able to clear both primary and secondary infections with Listeria monocytogenes. However, the kinetics of clearance was somewhat delayed in the absence of the VDR. Memory T cell development was not different in young VDR KO and wild-type (WT) mice; however, old VDR KO mice had significantly less memory T cells than their WT counterparts but still mounted an adequate immune response as determined by the complete clearance of L. monocytogenes. Although the primary and secondary immune responses were largely intact in the VDR KO mice, the old VDR KO mice had increased cytokines and antibody responses compared with the old WT mice. In particular, old VDR KO mice had elevated antigen non-specific antibodies; however, these magnified immune responses did not correspond to more effective Listeria clearance. The increased antibody and cytokine responses in the old VDR KO mice are consistent with the increased susceptibility of these mice to autoimmunity.