The genetic background influences the cellular and humoral immune responses to vaccines.
The genetic background influences the cellular and humoral immune responses to vaccines.
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遗传背景影响对疫苗的细胞和体液免疫反应。
DOI：
10.1111/cei.12841
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发表时间：
2016
影响因子：
4.6
通讯作者：
Nouri-Shirazi,M
中科院分区：
文献类型：
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作者：
Zeng,M;Nourishirazi,E;Guinet,E;Nouri-Shirazi,M
Toll样受体(TLR)激动剂作为诱导有效的T辅助细胞1型(Th1)免疫的候选佐剂的评估仍依赖于小鼠的使用。然而，近交系小鼠之间的遗传差异可能会影响佐剂的效果，并偏离研究结论。在这里，我们评估了用卵清蛋白(OVA)加明胶、TLR-3、TLR-4、TLR-7/8或TLR-9激动剂免疫的遗传不同的小鼠品系的细胞和体液反应的差异。我们发现，所有受试的TLR激动剂都显著地将树突状细胞(DC)和自然杀伤(NK)细胞招募到B6株的淋巴结中，促进了DC-NK的串扰，并增强了B6株的细胞反应。相反，TLR-3和TLR-7/8是仅有的两种在BALB/c株中显示细胞佐剂作用的激动剂。与其他TLR激动剂相比，TLR3和TLR7/8分别是在B6和BALBc株中产生干扰素γ产生效应的NK、CD4T细胞和CD8T细胞的最有效佐剂。我们还发现，与明矾相比，所有佐剂都更有效地在两个菌株中诱导B细胞的募集和OVA特异性免疫球蛋白(Ig)G2a的产生。此外，B6菌株招募了更多的B细胞，但令人惊讶的是，对所有佐剂的反应产生的OVA特异性IgG2a显著较低。然而，与免疫后在个别菌株中观察到的产生干扰素-γ的效应细胞的频率一致，我们在B6和BALB/c菌株的血清中分别检测到更多的卵清蛋白特异性IgG2a对TLR3和TLR7/8的反应。我们的数据表明，在评价TLR激动剂的活性以开发预防性和治疗性疫苗时，应考虑遗传背景。
The assessment of Toll-like receptor (TLR) agonists as candidate adjuvants for induction of effective T helper type 1 (Th1) immunity continues to rely on the use of mice. However, the genetic variation among inbred mice may influence the efficacy of adjuvants and bias a study's conclusions. Here, we evaluated the differences in cellular and humoral responses of genetically non-identical mouse strains immunized with ovalbumin (OVA) plus alum, TLR-3, TLR-4, TLR-7/8 or TLR-9 agonists. We found that all the tested TLR agonists recruited dendritic cells (DCs) and natural killer (NK) cells significantly into the lymph nodes, promoted DC–NK cross-talk and enhanced the cellular responses in B6 strain. In contrast, TLR-3 and TLR-7/8 were the only two agonists that showed the cellular adjuvanticity in the BALB/c strain. Compared with other TLR agonists, TLR-3 and TLR-7/8 were demonstrated to be the most effective adjuvants to generate interferon (IFN)-γ-producing effector NK, CD4, and CD8 T cells in B6 and BALB/c strains, respectively. We also found that compared with alum, all adjuvants induced the recruitment of B cells and production of OVA-specific immunoglobulin (Ig)G2a more effectively in both strains. In addition, the B6 strain recruited more B cells, but surprisingly produced significantly lower amounts of OVA-specific IgG2a in response to all adjuvants. However, consistent with the frequency of IFN-γ-producing effector cells observed in individual strains following immunizations, we detected more OVA-specific IgG2a in serum of B6 and BALB/c strains in response to TLR-3 and TLR-7/8, respectively. Our data suggest that genetic background should be taken into consideration when evaluating the activities of TLR agonists for the development of prophylactic and therapeutic vaccines.