Gold Marielle C, Donnelly Erin, Cook Matthew S, Leclair Catherine M, Lewinsohn Deborah A
Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.
Pediatr Res. 2006 Jul;60(1):34-7. doi: 10.1203/01.pdr.0000220352.13547.f4. Epub 2006 May 11.
Neonates are more susceptible than adults to viral and bacterial diseases. We hypothesized that plasmacytoid dendritic cells, the cells that provide large amounts of IFN-alpha in response to Toll-like receptor 9 (TLR9) agonists, are defective in neonates. To assess the intrinsic functionality of plasmacytoid dendritic cells from neonates we compared IFN-alpha production by plasmacytoid dendritic cells derived from neonates versus adults in both whole blood and in purified plasmacytoid dendritic cells. TLR9-stimulation of whole blood from adults and neonates resulted in comparable amounts of IFN-alpha production. However, we observed small but significant differences in IFN-alpha production from purified CD123+ plasmacytoid dendritic cells from neonates after stimulation with the TLR9 ligand CpG-DNA. Furthermore, we assessed surface expression of co-stimulatory molecules on plasmacytoid dendritic cells after stimulation. While purified CD123+ plasmacytoid dendritic cells from adults up-regulated co-stimulatory molecules CD80 and CD86 with IL-3 alone those from neonates required the addition of CpG-DNA to reach adult levels. Therefore, the intrinsic deficiencies of neonatal plasmacytoid dendritic cells can be mitigated by TLR9 agonists. These results are consistent with the observation that vaccines that effect strong adjuvant activity on dendritic cells can induce protective responses in neonates.
新生儿比成年人更容易感染病毒和细菌疾病。我们推测，浆细胞样树突状细胞，即能对Toll样受体9（TLR9）激动剂产生大量干扰素-α的细胞，在新生儿中存在缺陷。为了评估新生儿浆细胞样树突状细胞的内在功能，我们比较了来自新生儿和成年人的浆细胞样树突状细胞在全血和纯化的浆细胞样树突状细胞中产生干扰素-α的情况。用TLR9刺激成年人和新生儿的全血，产生的干扰素-α量相当。然而，在用TLR9配体CpG-DNA刺激后，我们观察到新生儿纯化的CD123+浆细胞样树突状细胞产生的干扰素-α存在微小但显著的差异。此外，我们评估了刺激后浆细胞样树突状细胞上共刺激分子的表面表达。虽然成年人纯化的CD123+浆细胞样树突状细胞仅用IL-3就能上调共刺激分子CD80和CD86，但新生儿的此类细胞需要添加CpG-DNA才能达到成年人的水平。因此，TLR9激动剂可以减轻新生儿浆细胞样树突状细胞的内在缺陷。这些结果与以下观察结果一致，即对树突状细胞具有强大佐剂活性的疫苗可以在新生儿中诱导保护性反应。
