Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice
Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice
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DOI：
10.1096/fj.11-190017
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发表时间：
2012-07-01
期刊：
影响因子：
4.8
通讯作者：
Badley, Andrew D.
中科院分区：
文献类型：
--
作者：
Cummins, Nathan W.;Weaver, Eric A.;Badley, Andrew D.
人们对流感感染严重程度和疫苗接种反应的个体差异的潜在机制知之甚少。我们研究了血红素加氧酶-1 (HO-1) 表达减少对疫苗反应和流感感染结果的影响。 HO-1 缺陷型和野生型 (WT) 小鼠（界、动物界；门、脊索动物；属/种、小家鼠）感染流感病毒 A/PR/8/34，事先接种或未接种基于腺病毒的流感疫苗。一项全基因组关联研究评估了 HO-1 基因中单核苷酸多态性 (SNP) 的表达以及健康人对流感疫苗接种的反应。与 WT 小鼠相比，HO-1 缺陷型小鼠在感染流感后存活率降低（中位存活期 5.5 天 vs. 6.5 天，P=0.016）。与 WT 小鼠相比，HO-1 缺陷小鼠在接种流感疫苗后抗体产生受损（平均抗体滴度 869 vs. 1698，P=0.02）。 HO-1 中的 1 个 SNP 和组成型表达同种型 HO-2 中的 1 个 SNP 与健康人类志愿者接种流感疫苗后抗体产生减少独立相关（P 分别为 0.017 和 0.014）。 HO-1 缺陷小鼠与性别和年龄匹配的 WT 对照配对。 HO-1 影响对流感感染和疫苗接种的免疫反应，表明治疗性诱导 HO-1 表达可能代表一种增强流感疫苗有效性的新型佐剂。-Cummins, N. W.、Weaver, E. A.、May, S. M.、Croatt, A. J.、Foreman, O.、Kennedy, R. B.、Poland, G. A.、Barry, M. A.、Nath, K. A.、Badley, A.D. Hemeoxygenase-1 调节老年小鼠对流感病毒感染和疫苗接种的免疫反应。 FASEB J. 26, 2911-2918 (2012)。 www.fasebj.org
Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median survival 5.5 vs. 6.5 d, P=0.016). HO-1-deficient mice had impaired production of antibody following influenza vaccination compared to WT mice (mean antibody titer 869 vs. 1698, P=0.02). One SNP in HO-1 and one SNP in the constitutively expressed isoform HO-2 were independently associated with decreased antibody production after influenza vaccination in healthy human volunteers (P=0.017 and 0.014, respectively). HO-1 deficient mice were paired with sex-and age-matched WT controls. HO-1 affects the immune response to both influenza infection and vaccination, suggesting that therapeutic induction of HO-1 expression may represent a novel adjuvant to enhance influenza vaccine effectiveness.-Cummins, N. W., Weaver, E. A., May, S. M., Croatt, A. J., Foreman, O., Kennedy, R. B., Poland, G. A., Barry, M. A., Nath, K. A., Badley, A. D. Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice. FASEB J. 26, 2911-2918 (2012). www.fasebj.org