IKKβ-induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector.
IKKβ-induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector.
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DOI：
10.1002/eji.201141910
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发表时间：
2012-03
影响因子：
5.4
通讯作者：
Beg, Amer A.
中科院分区：
文献类型：
--
作者：
Hopewell, Emily L.;Bronk, Crystina C.;Massengill, Michael;Engelman, Robert W.;Beg, Amer A.
疫苗中的微生物佐剂可激活关键转录因子，包括NF-κB和干扰素反应因子（irf）。然而，这些转录因子通路在佐剂促进适应性免疫中的个体作用尚不清楚。人们普遍认为，强烈炎症反应的诱导增强了适应性免疫反应。在这项研究中，我们试图确定激活促炎抑制剂κB激酶β (IKKβ)标准NF-κB通路是否促进疫苗诱导的免疫应答。与对照病毒相比，一种表达组成型激活IKKβ (AdIKK)的腺病毒诱导了DC成熟和关键细胞因子的高表达。在体内，AdIKK触发肺部感染后的快速炎症，增加白细胞进入引流LNs，并增强早期抗体和t细胞反应。值得注意的是，AdIKK不影响适应性免疫反应的总体程度。这些结果表明，在这种情况下，IKKβ/NF-κB诱导炎症影响动力学，但不影响适应性免疫反应的大小。因此，这些发现有助于确定疫苗佐剂诱导的关键途径在促进适应性免疫中的个体作用。
Microbial adjuvants in vaccines activate key transcription factors, including NF-κB and interferon response factors (IRFs). However, the individual role of these transcription factor pathways in promoting adaptive immunity by adjuvants is not clear. It is widely believed that induction of a strong inflammatory response potentiates an adaptive immune response. In this study, we sought to determine whether activation of the pro-inflammatory inhibitor of κB kinase β (IKKβ) canonical NF-κB pathway promoted vaccine-induced immune responses. An adenovirus expressing constitutively-activated IKKβ (AdIKK) induced robust DC maturation and high expression of key cytokines compared to a control virus. In vivo, AdIKK triggered rapid inflammation after pulmonary infection, increased leukocyte entry into draining LNs, and enhanced early antibody and T-cell responses. Notably, AdIKK did not influence the overall magnitude of the adaptive immune response. These results indicate that induction of inflammation by IKKβ/NF-κB in this setting impacts the kinetics but not the magnitude of adaptive immune responses. These findings therefore help define the individual role of a key pathway induced by vaccine adjuvants in promoting adaptive immunity.
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影响因子：
5.4
作者：
Chan, Gary;Bivins-Smith, Elizabeth R.;Yurochko, Andrew D.
通讯作者：
Yurochko, Andrew D.
DOI：
10.1073/pnas.0603493103
发表时间：
2006-09-26
影响因子：
11.1
作者：
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作者：
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影响因子：
64.8
作者：
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通讯作者：
Pulendran, Bali