Specific antibodies protect gamma-irradiated mice against Francisella tularensis infection

Specific antibodies protect gamma-irradiated mice against Francisella tularensis infection
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DOI:
10.1016/j.micpath.2012.07.006
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发表时间:
2012-11-01
影响因子:
3.8
通讯作者:
Macela, Ales
Macela, Ales
中科院分区:
医学3区
文献类型:
--
作者:
Kubelkova, Klara;Krocova, Zuzana;Macela, Ales

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抗体在土拉弗朗西斯菌(F.土拉热)感染仍然是一个争论的主题。了解体液免疫的作用是非常重要的努力,以发展有效的预防措施,对感染弗朗西斯菌强毒株。我们利用γ射线照射小鼠模型研究抗土拉菌抗体的保护作用,以部分消除细胞反应。γ射线照射小鼠模型也可以证明免疫受损宿主对细胞内细菌感染的反应。剂量大于3戈伊的γ-照射完全损害小鼠对感染的抵抗力,并导致细胞因子产生的失衡。在这项研究中,我们证明了被动转移免疫血清保护辐射小鼠免受随后的感染与菌株的F。土拉热亚种全北极星将BALB/c或C3 H/CBi株的未处理小鼠进行从用活疫苗株(LVS)F免疫的小鼠获得的血清的被动转移。tularensis LVS、F.土拉热亚种holarctica菌株15、热灭活F.土拉热菌LVS,或在用致死剂量的LVS或菌株15感染前两小时热灭活的菌株15。从免疫小鼠获得的血清的被动转移赋予了未受照射的幼稚小鼠以及亚致死剂量照射的小鼠对低致死剂量的F.土拉热菌LVS或菌株15。此外,被动保护的小鼠在初次感染F。土拉热菌LVS也能抵抗进一步的高毒力F.土拉热亚种土拉菌4.此外,证明了通过特异性抗血清成功的被动免疫转移和随后的免疫功能低下动物的主动免疫的组合的第一个证据。总之,我们证明了B细胞介导的效应反应与T.细胞介导的免疫在未处理的小鼠和免疫受损的小鼠中都起重要作用,并且在设计新疫苗时考虑这一事实是适当的。(c)2012爱思唯尔有限公司保留所有权利。
The role of antibodies in the course of Francisella tularensis (F. tularensis) infection is still a subject of debate. The understanding of the poorly described role of humoral immunity is more than important for the effort to develop effective prophylactic procedure against the infection with Francisella virulent strains. We utilized the model of gamma-irradiated mice for the studies of the protective role of anti-tularensis antibodies in order to partially eliminate cellular responses. The model of gamma-irradiated mice can also demonstrate the responses of immunocompromised host to intracellular bacterial infection. The gamma-irradiation by doses greater than 3 Gy completely impairs the resistance to infection and causes a disbalance of cytokine production in mice. In this study, we demonstrate that passive transfer of immune sera protected irradiated mice against subsequent infection with strains of F. tularensis subsp. holarctica. Naive mice of BALB/c or C3H/CBi strains were subjected to passive transfer of sera obtained from immunized mice with live vaccine strain (LVS) F. tularensis LVS, F. tularensis subsp. holarctica strain 15, heat-killed F. tularensis LVS, or heat-killed strain 15 two hours before infection with lethal doses of LVS or strain 15. The passive transfer of sera obtained from immunized mice conferred full protection of naive unirradiated as well as sublethally irradiated mice against low lethal doses of infection with F. tularensis LVS or strain 15, in all variants of the experiments. In addition, the passively protected mice that survived the primary infection with F. tularensis LVS were protected also against further secondary challenge with a highly virulent strain of F. tularensis subsp. tularensis SchuS4. Moreover, the first evidence of combination of successful passive transfer of immunity by specific antisera and subsequent active immunization of immunocompromised animals is demonstrated. In summary, we demonstrate that B cell-mediated effector responses together with the induction of T. cell-mediated immunity both play an important role in naive and also in immunocompromised mice and this fact it would be appropriate to take into the account in the design of new vaccines. (c) 2012 Elsevier Ltd. All rights reserved.