Francisella tularensis type B ΔdsbA mutant protects against type A strain and induces strong inflammatory cytokine and Th1-like antibody response in vivo.
Francisella tularensis type B ΔdsbA mutant protects against type A strain and induces strong inflammatory cytokine and Th1-like antibody response in vivo.
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土拉弗朗西斯菌 B 型 ΔdsbA 突变体可预防 A 型菌株，并在体内诱导强烈的炎症细胞因子和 Th1 样抗体反应。
DOI：
10.1093/femspd/ftv058
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发表时间：
2015
影响因子：
3.3
通讯作者：
J. Stulík
中科院分区：
文献类型：
--
作者：
A. Strašková;P. Spidlova;S. Mou;P. Worsham;Daniela Putzová;I. Pavkova;J. Stulík
土拉弗朗西斯菌土拉菌亚种是一种高毒力的细胞内细菌病原体，引起土拉菌病。然而，目前尚未开发出安全有效的常规疫苗来对抗土拉弗拉菌。我们最近在 B 型土拉弗拉菌亚种中构建了 DsbA 同源蛋白 (ΔdsbA/FSC200) 和假设蛋白 IglH (ΔiglH/FSC200) 的缺失突变体。 holarctica FSC200菌株，对亲本强毒株发挥不同的保护能力。在这项研究中，我们进一步研究了 ΔdsbA/FSC200 和 ΔiglH/FSC200 突变体提供的这些不同水平的保护的免疫学相关性。我们的结果表明，ΔdsbA/FSC200 突变体（而非 ΔiglH/FSC200 突变体）诱导早期先天炎症反应，导致强烈的 Th1 样抗体反应。此外，接种ΔdsbA/FSC200突变体，但不接种ΔiglH/FSC200，可在小鼠中引发针对随后A型SCHU S4菌株攻击的保护作用。使用免疫蛋白质组学方法绘制了 Th1 样特异性抗体靶向的一系列抗原图谱，并鉴定了 80 多种细菌抗原，包括新抗原。疫苗接种后 ΔdsbA/FSC200 识别的土拉菌抗原与攻毒后 SCHU S4 血清的比较揭示了 22 个新型 SCHU S4 特异性抗体克隆的存在。
Francisella tularensis subspecies tularensis is a highly virulent intracellular bacterial pathogen, causing the disease tularemia. However, a safe and effective vaccine for routine application against F. tularensis has not yet been developed. We have recently constructed the deletion mutants for the DsbA homolog protein (ΔdsbA/FSC200) and a hypothetical protein IglH (ΔiglH/FSC200) in the type B F. tularensis subsp. holarctica FSC200 strain, which exerted different protection capacity against parental virulent strain. In this study, we further investigated the immunological correlates for these different levels of protection provided by ΔdsbA/FSC200 and ΔiglH/FSC200 mutants. Our results show that ΔdsbA/FSC200 mutant, but not ΔiglH/FSC200 mutant, induces an early innate inflammatory response leading to strong Th1-like antibody response. Furthermore, vaccination with ΔdsbA/FSC200 mutant, but not with ΔiglH/FSC200, elicited protection against the subsequent challenge with type A SCHU S4 strain in mice. An immunoproteomic approach was used to map a spectrum of antigens targeted by Th1-like specific antibodies, and more than 80 bacterial antigens, including novel ones, were identified. Comparison of tularemic antigens recognized by the ΔdsbA/FSC200 post-vaccination and the SCHU S4 post-challenge sera then revealed the existence of 22 novel SCHU S4 specific antibody clones.
影响因子：
3.8
作者：
Thathiah, Prea;Sanapala, Shilpa;Rodriguez, Annette R.;Yu, Jieh-Juen;Murthy, Ashlesh K.;Guentzel, M. Neal;Forsthuber, Thomas G.;Chambers, James P.;Arulanandam, Bernard P.
通讯作者：
Arulanandam, Bernard P.
影响因子：
4.4
作者：
Balonova, Lucie;Hernychova, Lenka;Mann, Benjamin F.;Link, Marek;Bilkova, Zuzana;Novotny, Milos V.;Stulik, Jiri
通讯作者：
Stulik, Jiri