Vitamin A Deficiency Disrupts Vaccine-Induced Antibody-Forming Cells and the Balance of IgA/IgG Isotypes in the Upper and Lower Respiratory Tract
Vitamin A Deficiency Disrupts Vaccine-Induced Antibody-Forming Cells and the Balance of IgA/IgG Isotypes in the Upper and Lower Respiratory Tract
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DOI：
10.1089/vim.2012.0023
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发表时间：
2012-08-01
期刊：
影响因子：
2.2
通讯作者：
Hurwitz, Julia L.
中科院分区：
文献类型：
--
作者：
Surman, Sherri L.;Rudraraju, Rajeev;Hurwitz, Julia L.
通过鼻内（IN）接种具有复制能力的病毒进行疫苗接种形成了获得许可的新型候选呼吸道病毒疫苗（例如冷适应流感病毒疫苗）的基础。疫苗接种对全球的积极影响取决于饮食缺陷普遍存在的发展中国家的疫苗功效。目前的研究设计使用仙台病毒 (SeV) 作为模型呼吸道病毒疫苗，以测试维生素 A 缺乏 (VAD) 情况下抗体形成细胞 (AFC) 的驻留和同种型表达。接种疫苗后 1 个月采集样本，此时健康动物的 AFC 通常达到峰值。在健康饮食的对照动物中，SeV 诱导抗体反应，相对偏向于上呼吸道中的 IgA（URT，通过鼻洗液取样）和下呼吸道中的 IgG（LRT，通过支气管肺泡灌洗 [BAL] 取样）。在 VAD 的背景下，鼻洗液中 SeV 特异性 IgA 抗体显着减少，有利于 BAL 中增强的 IgG 抗体。当检查弥漫性鼻相关淋巴组织 (d-NALT)、肺、颈淋巴结 (CLN) 和纵隔淋巴结 (MLN) 中的 AFC 时，出现了类似的模式。 AFC 在 d-NALT 中最常见，在对照小鼠中 IgA 表达最多。在 VAD 的背景下，这些产生 IgA 的 AFC 数量显着减少，从而扭曲了 IgA 和 IgG 的自然平衡。综上所述，结果表明，众所周知，VAD 饮食与肠道免疫缺陷有关，它显着改变了呼吸道中 AFC 的诱导和同型表达。
Vaccination by intranasal (IN) inoculation with a replication-competent virus forms the basis of licensed and novel candidate respiratory viral vaccines (e. g., the cold-adapted influenza virus vaccine). A positive global impact of vaccination depends on vaccine efficacy in developing countries where dietary deficiencies are commonplace. The current study was designed using Sendai virus (SeV) as a model respiratory viral vaccine to test antibody-forming cell (AFC) residence and isotype expression in the context of a vitamin A deficiency (VAD). Samples were taken 1 mo after vaccination when AFCs generally reach their peak in healthy animals. In control animals on a healthy diet, SeV induced an antibody response with a relative bias toward IgA in the upper respiratory tract (URT, as sampled by nasal wash), and IgG in the lower respiratory tract (LRT, as sampled by bronchoalveolar lavage [BAL]). In the context of VAD, the SeV-specific IgA antibodies in the nasal wash were significantly reduced in favor of enhanced IgG antibodies in the BAL. When AFCs were examined in diffuse nasal-associated lymphoid tissues (d-NALT), lungs, cervical lymph nodes (CLN), and mediastinal lymph nodes (MLN), a similar pattern emerged. AFCs were most frequent in the d- NALT and most expressed IgA in control mice. In the context of VAD, these IgA-producing AFCs were significantly reduced in number, skewing the natural balance of IgA and IgG. Taken together, the results show that the VAD diet, which is well known for its association with immune defects in the gut, significantly alters AFC induction and isotype expression in the respiratory tract.