Evaluation of innate immunity and vector toxicity following inoculation of bovine, porcine or human adenoviral vectors in a mouse model.
Evaluation of innate immunity and vector toxicity following inoculation of bovine, porcine or human adenoviral vectors in a mouse model.
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DOI：
10.1016/j.virusres.2010.07.021
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发表时间：
2010-10
期刊：
影响因子：
5
通讯作者：
Mittal, Suresh K.
中科院分区：
文献类型：
--
作者：
Sharma, Anurag;Bangari, Dinesh S.;Tandon, Manish;HogenEsch, Harm;Mittal, Suresh K.
关键词：
来源于牛Ad血清3型（BAd3）或猪Ad血清3型（PAd3）的非人腺病毒（Ad）载体可以绕过预先存在的对人Ad （HAd）的免疫。我们之前已经报道了这些Ad载体对人类和非人类细胞的不同转导，以及它们不同的受体使用和生物分布。为了比较小鼠静脉注射PAd3、BAd3或HAd5载体后库普弗细胞（KCs）对先天免疫、载体毒性和载体摄取的诱导，我们测定了肝脏和脾脏中促炎趋化因子和细胞因子以及toll样受体（TLRs）的mRNA表达水平。通过比较血清肝脏特异性酶水平、组织病理学和库普弗细胞（KC）损耗来评估这些载体的组织毒性。与HAd5载体相比，PAd3和BAd3载体的TLRs、促炎趋化因子和细胞因子基因的mRNA表达增强，表明它们能更有效地刺激先天免疫反应。肝脏组织病理学改变在接种had5的小鼠中最为明显，而接种BAd3或pad3的小鼠仅在早期时间点出现轻度组织学改变。接种ha5或PAd3载体可显著降低肝脏中KCs的数量（P <0.05）。总之，这些结果扩展了我们之前关于非人类和人类Ad载体不同体内生物学的观察。
Nonhuman adenovirus (Ad) vectors derived from bovine Ad serotype 3 (BAd3) or porcine Ad serotype 3 (PAd3) can circumvent pre-existing immunity against human Ad (HAd). We have previously reported differential transduction of human and nonhuman cells by these Ad vectors, and their distinct receptor usage and biodistribution. To compare the induction of innate immunity, vector toxicity and vector uptake by Kupffer cells (KCs) following intravenous administration of PAd3, BAd3, or HAd5 vectors in mice, we determined mRNA expression levels of proinflammatory chemokines and cytokines, and Toll-like receptors (TLRs) in the liver and spleen. Tissue toxicity of these vectors was assessed by comparing serum levels of liver-specific enzymes, histopathology and Kupffer cell (KC) depletion. Compared to the HAd5 vector, PAd3 and BAd3 vectors were more potent stimulators of innate immune responses as indicated by enhanced mRNA expression of TLRs and proinflammatory chemokines and cytokine genes. Histopathological changes in the liver were most pronounced in HAd5-inoculated mice while BAd3- or PAd3-inoculated mice revealed mild histologic changes that were confined to early time points. Inoculation with HAd5 or PAd3 vectors resulted in a significant (P <0.05) decline of the number of KCs in the liver. Together, these results extend our previous observations regarding distinct in vivo biology of nonhuman and human Ad vectors.
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影响因子：
5.5
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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