Downmodulation of vaccine-induced immunity and protection against the intracellular bacterium Francisella tularensis by the inhibitory receptor FcγRIIB.
Downmodulation of vaccine-induced immunity and protection against the intracellular bacterium Francisella tularensis by the inhibitory receptor FcγRIIB.
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DOI：
10.1155/2015/840842
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发表时间：
2015
影响因子：
4.1
通讯作者：
Gosselin EJ
中科院分区：
文献类型：
--
作者：
Franz BJ;Li Y;Bitsaktsis C;Iglesias BV;Pham G;Sunagar R;Kumar S;Gosselin EJ
Fc γ受体IIB（FcγRIIB）是唯一一种在与抗原-（Ag-）抗体（Ab）复合物接合时负调节免疫反应的Fc γ受体（FcγR）。因此，响应于感染或免疫的Ag特异性IgG的产生具有下调针对感染的免疫保护的潜力。因此，我们试图确定FcγRIIB对针对土拉热弗朗西丝菌（Ft）（A类生物威胁因子）的免疫保护的影响。我们利用灭活的Ft（iFt）作为免疫原。用Ft活疫苗株（LVS）攻毒未经处理和iFt免疫的FcγRIIB敲除（KO）或野生型（WT）小鼠。虽然未处理FcγRIIB KO与WT小鼠之间的存活率未观察到显著差异，但iFT免疫的FcγRIIB KO小鼠的保护效果显著优于iFT免疫的WT小鼠。血清和支气管肺泡灌洗液中的FT特异性伊加以及从iFT免疫的FcγRIIB KO收获的脾细胞产生的IFN-γ、IL-10和TNF-α也显著升高。此外，iFT免疫FcγRIIB KO小鼠在攻毒后5天表现出体内促炎细胞因子水平降低，这与已发表研究中Ft-LVS攻毒后存活率增加相关。因此，这些研究首次证明了FcγRIIB调节疫苗诱导的伊加产生并下调免疫和保护的能力。上述观察结果背后的免疫机制及其对疫苗开发的潜在影响进行了讨论。
Fc gamma receptor IIB (FcγRIIB) is the only Fc gamma receptor (FcγR) which negatively regulates the immune response, when engaged by antigen- (Ag-) antibody (Ab) complexes. Thus, the generation of Ag-specific IgG in response to infection or immunization has the potential to downmodulate immune protection against infection. Therefore, we sought to determine the impact of FcγRIIB on immune protection against Francisella tularensis (Ft), a Category A biothreat agent. We utilized inactivated Ft (iFt) as an immunogen. Naïve and iFt-immunized FcγRIIB knockout (KO) or wildtype (WT) mice were challenged with Ft-live vaccine strain (LVS). While no significant difference in survival between naïve FcγRIIB KO versus WT mice was observed, iFt-immunized FcγRIIB KO mice were significantly better protected than iFt-immunized WT mice. Ft-specific IgA in serum and bronchial alveolar lavage, as well as IFN-γ, IL-10, and TNF-α production by splenocytes harvested from iFt-immunized FcγRIIB KO, were also significantly elevated. In addition, iFt-immunized FcγRIIB KO mice exhibited a reduction in proinflammatory cytokine levels in vivo at 5 days after challenge, which correlates with increased survival following Ft-LVS challenge in published studies. Thus, these studies demonstrate for the first time the ability of FcγRIIB to regulate vaccine-induced IgA production and downmodulate immunity and protection. The immune mechanisms behind the above observations and their potential impact on vaccine development are discussed.
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影响因子：
3.8
作者：
Kubelkova, Klara;Krocova, Zuzana;Macela, Ales
通讯作者：
Macela, Ales
影响因子：
4.6
作者：
Goodman, Anna L.;Forbes, Emily K.;Williams, Andrew R.;Douglas, Alexander D.;de Cassan, Simone C.;Bauza, Karolis;Biswas, Sumi;Dicks, Matthew D. J.;Llewellyn, David;Moore, Anne C.;Janse, Chris J.;Franke-Fayard, Blandine M.;Gilbert, Sarah C.;Hill, Adrian V. S.;Pleass, Richard J.;Draper, Simon J.
通讯作者：
Draper, Simon J.
DOI：
10.1196/annals.1409.012
发表时间：
2007-01-01
期刊：
FRANCISELLA TULARENSIS: BIOLOGY, PATHOGENICITY, EPIDEMIOLOGY, AND BIODEFENSE
影响因子：
--
作者：
Conlan, J. Wayne;Oyston, Petra C. F.
通讯作者：
Oyston, Petra C. F.
DOI：
10.1073/pnas.0813411106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Cole, Leah E.;Yang, Yang;Vogel, Stefanie N.
通讯作者：
Vogel, Stefanie N.
影响因子：
3.1
作者：
Dreisbach, VC;Cowley, S;Elkins, KL
通讯作者：
Elkins, KL