Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low Sensitization to Infection.
Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low Sensitization to Infection.
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肿瘤坏死因子-α 靶向可以预防对感染低敏感性的关节炎。
DOI：
10.3389/fimmu.2017.01533
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发表时间：
2017
影响因子：
7.3
通讯作者：
Assier E
中科院分区：
文献类型：
--
作者：
Belmellat N;Semerano L;Segueni N;Damotte D;Decker P;Ryffel B;Quesniaux V;Boissier MC;Assier E
肿瘤坏死因子-α（TNF-α）阻断是类风湿性关节炎（RA）和其他炎症性疾病的有效治疗方法，但在患者中，它与对结核分枝杆菌和单核细胞增生李斯特菌等传染性病原体的耐药性降低有关。我们的目标是在小鼠中建立感染和关节炎模型，并将目前使用的抗TNF-α抑制剂依那西普与抗TNF-α疫苗进行比较。我们开发了TNF-α类激酶的鼠替代物，并产生了由与TNF-α偶联的钥孔血蓝蛋白组成的抗鼠TNF-α疫苗（TNFKi），其导致小鼠产生抗TNF-α抗体。我们还使用依那西普（一种常用于治疗RA的可溶性TNF受体）作为TNF中和的对照。在胶原诱导的关节炎小鼠模型中，TNFKi对炎症的保护作用与依那西普相似。在急性L.在单核细胞增多症感染后，所有TNFKi治疗的小鼠显示清除的细菌感染并存活，而依那西普治疗的小鼠显示大的肝肉芽肿并迅速死亡。此外，TNFKi小鼠感染强毒H37 Rv M.与依那西普治疗的小鼠或对照相比，结核病显示出对感染的抗性。根据TNF-α阻断策略，使用TNF-α抑制剂治疗关节炎可能导致不同的感染易感性特征。我们的TNFKi疫苗允许比依那西普更好的剩余宿主防御。
Tumor necrosis factor-alpha (TNF-α) blockade is an effective treatment for rheumatoid arthritis (RA) and other inflammatory diseases, but in patients, it is associated with reduced resistance to the infectious agents Mycobacterium tuberculosis and Listeria monocytogenes, among others. Our goal was to model infection and arthritis in mice and to compare etanercept, a currently used anti-TNF-α inhibitor, to an anti-TNF-α vaccine. We developed a murine surrogate of the TNF-α kinoid and produced an anti-murine TNF-α vaccine (TNFKi) composed of keyhole limpet hemocyanin conjugated to TNF-α, which resulted in anti-TNF-α antibody production in mice. We also used etanercept (a soluble receptor of TNF commonly used to treat RA) as a control of TNF neutralization. In a mouse model of collagen-induced arthritis, TNFKi protected against inflammation similar to etanercept. In a mouse model of acute L. monocytogenes infection, all TNFKi-treated mice showed cleared bacterial infection and survived, whereas etanercept-treated mice showed large liver granulomas and quickly died. Moreover, TNFKi mice infected with the virulent H37Rv M. tuberculosis showed resistance to infection, in contrast with etanercept-treated mice or controls. Depending on the TNF-α blockade strategy, treating arthritis with a TNF-α inhibitor could result in a different profile of infection suceptibility. Our TNFKi vaccine allowed for a better remaining host defense than did etanercept.
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影响因子：
5.8
作者：
Fremond C;Allie N;Dambuza I;Grivennikov SI;Yeremeev V;Quesniaux VF;Jacobs M;Ryffel B
通讯作者：
Ryffel B
影响因子：
3.2
作者：
Dambuza, I.;Allie, N.;Jacobs, M.
通讯作者：
Jacobs, M.
影响因子：
158.5
作者：
Keane, J;Gershon, S;Braun, MM
通讯作者：
Braun, MM
影响因子：
3.2
作者：
Bourigault, Marie-Laure;Segueni, Noria;Quesniaux, Valerie F. J.
通讯作者：
Quesniaux, Valerie F. J.
DOI：
10.1073/pnas.94.10.5243
发表时间：
1997-05-13
影响因子：
11.1
作者：
MacMicking, JD;North, RJ;Nathan, CF
通讯作者：
Nathan, CF