College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.
Int Immunopharmacol. 2010 Oct;10(10):1249-60. doi: 10.1016/j.intimp.2010.07.006. Epub 2010 Jul 29.
CpG oligodeoxynucleotide (CpG ODN) has been described as an effective activator of the innate immune system, with potential to protect against infection caused by a range of pathogens in a non-specific manner. We therefore investigated if intranasal (IN), oral (OR)-mucosal, and intramuscular (IM)-systemic administrations of CpG ODN without antigen codelivery could all enhance innate immunity in the enteric mucosa and control the extent of enterotoxigenic Escherichia coli (ETEC) infection in weaning piglets. Here our data showed that CpG ODN dosed by IN, OR or IM routes protected weaning piglets against a subsequent challenge with ETEC. The level of protection was greater when CpG ODN was administered IN and OR than IM, demonstrating a clear relationship between the route of CpG dosing and protection. IN and OR treatments with CpG ODN reduced bacterial load in the phases at days 3-5 post challenge. The CXC chemokine (CXCL10 and CXCL11) and CC chemokine (CCL4 and CCL5) mRNA expressions were elevated in the intestinal tissues from animals treated IN or OR with CpG ODN compared to untreated controls. Significantly enhanced mRNA expressions for cathelicidins (PR-39 and protegrin-1), but moderately for β-defensin (pBD1 and pBD2), were observed in IN or OR CpG-treatments. Also, significant production of cytokines (IL-12, IFN-γ, and MCP-1) and F4-specific antibodies (IgG/IgA) was detected in intestinal washings following IN and OR CpG-treatments. In contrast, IM delivery induced marked production of sera F4-specific antibodies. It was possible that these chemokines, cytokines, cathelicidins and antibodies played a role in the clearance of ETEC. These findings suggested that IN or OR administration of CpG ODN without antigen codelivery might represent a valuable strategy for induction of innate immunity against ETEC infection.
CpG 寡脱氧核苷酸（CpG ODN）已被描述为一种有效的先天免疫系统激活剂，具有以非特异性方式保护免受多种病原体感染的潜力。因此，我们研究了在不伴随抗原共给药的情况下，经鼻腔（IN）、口服（OR）-黏膜和肌肉内（IM）-全身给予 CpG ODN 是否都能增强肠黏膜中的固有免疫，并控制断奶仔猪中肠产毒性大肠杆菌（ETEC）感染的程度。我们的数据表明，通过 IN、OR 或 IM 途径给予 CpG ODN 可保护断奶仔猪免受随后的 ETEC 挑战。当 CpG ODN 通过 IN 和 OR 给药时，其保护水平高于 IM，这表明 CpG 给药途径与保护之间存在明显关系。IN 和 OR 用 CpG ODN 处理可降低攻毒后第 3-5 天的细菌负荷。与未处理对照组相比，IN 或 OR 用 CpG ODN 处理的动物的肠道组织中 CXC 趋化因子（CXCL10 和 CXCL11）和 CC 趋化因子（CCL4 和 CCL5）mRNA 表达升高。在 IN 或 OR CpG 处理中观察到 cathelicidins（PR-39 和 protegrin-1）的 mRNA 表达显著增强，但β-defensin（pBD1 和 pBD2）的 mRNA 表达适度增强。此外，在 IN 或 OR CpG 处理后，还检测到细胞因子（IL-12、IFN-γ 和 MCP-1）和 F4 特异性抗体（IgG/IgA）在肠灌洗液中的显著产生。相比之下，IM 给药诱导了明显的血清 F4 特异性抗体产生。这些趋化因子、细胞因子、cathelicidins 和抗体可能在清除 ETEC 中发挥作用。这些发现表明，在不伴随抗原共给药的情况下，经 IN 或 OR 给予 CpG ODN 可能代表一种诱导针对 ETEC 感染的固有免疫的有价值策略。
