Laboratory of Inflammation, Gestation and Autoimmunity, Jacques Monod Institute, CNRS and University Paris-Diderot, 15 rue Hélène Brion, 75205 Paris Cedex 13, France; Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University UM2, France; INSERM U1104 and CNRS UMR7280, Marseille, France.
Microbes Infect. 2013 Nov;15(13):928-38. doi: 10.1016/j.micinf.2013.08.006. Epub 2013 Aug 31.
Invariant CD1d-restricted natural killer T cells play an important immunoregulatory role and can influence a broad spectrum of immunological responses including against bacterial infections. They are present at the fetal-maternal interface and although it has been reported that experimental systemic iNKT cell activation can induce mouse abortion, their role during pregnancy remain poorly understood. In the present work, using a physiological Chlamydia muridarum infection model, we have shown that, in vaginally infected pregnant mice, C. muridarum is cleared similarly in C57BL/6 wild type (WT) and CD1d(-/-) mice. We have also shown that infected- as well as uninfected-CD1d(-/-) mice have the same litter size as WT counterparts. Thus, CD1d-restricted cells are required neither for the resolution of chlamydial infection of the lower-genital tract, nor for the maintenance of reproductive capacity. However, unexpected differences in T cell populations were observed in uninfected pregnant females, as CD1d(-/-) placentas contained significantly higher percentages of CD4(+) and CD8(+) T cells than WT counterparts. However, infection triggered a significant decrease in the percentages of CD4(+) T cells in CD1d(-/-) mice. In infected WT pregnant mice, the numbers of uterine CD4(+) and CD8(+) T cells, monocytes and granulocytes were greatly increased, changes not observed in infected CD1d(-/-) mice. An increase in the percentage of CD8(+) T cells seems independent of CD1d-restricted cells as it occurred in both WT and CD1d(-/-) mice. Thus, in the steady state, the lack of CD1d-restricted NKT cells affects leukocyte populations only in the placenta. In Chlamydia-infected pregnant mice, the immune response against Chlamydia is dampened in the uterus. Our results suggest that CD1d-restricted NKT cells play a role in the recruitment or homeostasis of leukocyte populations at the maternal-fetal interface in the presence or absence of Chlamydia infection.
不变的 CD1d 限制性自然杀伤 T 细胞发挥着重要的免疫调节作用,可以影响广泛的免疫反应,包括对抗细菌感染。它们存在于胎儿-母体界面,尽管已经报道实验性系统性 iNKT 细胞激活可诱导小鼠流产,但它们在怀孕期间的作用仍知之甚少。在本工作中,我们使用生理沙眼衣原体感染模型表明,在阴道感染的怀孕小鼠中,C. muridarum 在 C57BL/6 野生型(WT)和 CD1d(-/-)小鼠中被清除的方式相似。我们还表明,感染和未感染的 CD1d(-/-)小鼠的产仔数与 WT 小鼠相同。因此,CD1d 限制性细胞既不需要解决下生殖道的衣原体感染,也不需要维持生殖能力。然而,在未感染的怀孕雌性中观察到 T 细胞群体的意外差异,因为 CD1d(-/-)胎盘中的 CD4(+)和 CD8(+)T 细胞百分比明显高于 WT 对应物。然而,感染导致 CD1d(-/-)小鼠中 CD4(+)T 细胞的百分比显著下降。在感染 WT 怀孕小鼠中,子宫 CD4(+)和 CD8(+)T 细胞、单核细胞和粒细胞的数量大大增加,而在感染 CD1d(-/-)小鼠中未观察到这些变化。CD8(+)T 细胞的百分比增加似乎与 CD1d 限制性细胞无关,因为它发生在 WT 和 CD1d(-/-)小鼠中。因此,在稳态下,缺乏 CD1d 限制性 NKT 细胞仅影响胎盘中的白细胞群体。在感染沙眼衣原体的怀孕小鼠中,子宫对沙眼衣原体的免疫反应受到抑制。我们的结果表明,CD1d 限制性 NKT 细胞在存在或不存在衣原体感染的情况下,在母体-胎儿界面处白细胞群体的募集或动态平衡中发挥作用。