A Combination of Flt3 Ligand cDNA and CpG Oligodeoxynucleotide as Nasal Adjuvant Elicits Protective Secretory-IgA Immunity to Streptococcus pneumoniae in Aged Mice
A Combination of Flt3 Ligand cDNA and CpG Oligodeoxynucleotide as Nasal Adjuvant Elicits Protective Secretory-IgA Immunity to Streptococcus pneumoniae in Aged Mice
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DOI：
10.4049/jimmunol.1002837
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发表时间：
2011-02-15
影响因子：
4.4
通讯作者：
Fujihashi, Kohtaro
中科院分区：
文献类型：
--
作者：
Fukuyama, Yoshiko;King, Janice D.;Fujihashi, Kohtaro
我们之前的研究表明，将表达质粒的 Flt3 配体 (pFL) 和 CpG 寡脱氧核苷酸 (CpG ODN) 组合作为组合鼻佐剂，可在老年（2 岁）小鼠中引发粘膜免疫反应。在本研究中，我们研究了 pFL 和 CpG ODN 组合作为肺炎球菌表面蛋白 A (PspA) 的鼻佐剂是否会增强 PspA 特异性分泌型 IgA Ab 反应，从而为老年小鼠提供针对肺炎链球菌感染的保护性粘膜免疫。使用 PspA 加上 pFL 和 CpG ODN 组合进行鼻免疫，在年轻成年和老年小鼠的外部分泌物和血浆中引起 PspA 特异性分泌型 IgA Ab 反应水平升高。在老年小鼠的鼻咽相关淋巴网状组织、颈部淋巴结和脾脏中，观察到显着水平的 PspA 特异性 CD4(+) T 细胞增殖和 PspA 诱导的 Th1 和 Th2 型细胞因子应答，与年轻成年小鼠的水平相当。此外，在老年小鼠的粘膜诱导和效应淋巴组织中检测到表达成熟型 CD8、CD11b 的树突状细胞数量增加。重要的是，给予 PspA 加 pFL 和 CpG ODN 组合的老年小鼠显示出针对鼻腔肺炎链球菌定植的保护性免疫力。这些结果表明，鼻腔递送组合 DNA 佐剂为预防老年人肺炎链球菌提供了一种有吸引力的可能性。免疫学杂志，2011，186：2454-2461。
Our previous study showed that a combination of a plasmid-expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotides (CpG ODN) as a combined nasal adjuvant elicited mucosal immune responses in aged (2-y-old) mice. In this study, we investigated whether a combination of pFL and CpG ODN as a nasal adjuvant for a pneumococcal surface protein A (PspA) would enhance PspA-specific secretory-IgA Ab responses, which could provide protective mucosal immunity against Streptococcus pneumoniae infection in aged mice. Nasal immunization with PspA plus a combination of pFL and CpG ODN elicited elevated levels of PspA-specific secretory-IgA Ab responses in external secretions and plasma in both young adult and aged mice. Significant levels of PspA-specific CD4(+) T cell proliferative and PspA-induced Th1- and Th2-type cytokine responses were noted in nasopharyngeal-associated lymphoreticular tissue, cervical lymph nodes, and spleen of aged mice, which were equivalent to those in young adult mice. Additionally, increased numbers of mature-type CD8, CD11b-expressing dendritic cells were detected in mucosal inductive and effector lymphoid tissues of aged mice. Importantly, aged mice given PspA plus a combination of pFL and CpG ODN showed protective immunity against nasal S. pneumoniae colonization. These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for protection against S. pneumoniae in the elderly. The Journal of Immunology, 2011, 186: 2454-2461.