Outer membrane vesicles derived from Salmonella Typhimurium mutants with truncated LPS induce cross-protective immune responses against infection of Salmonella enterica serovars in the mouse model.
Outer membrane vesicles derived from Salmonella Typhimurium mutants with truncated LPS induce cross-protective immune responses against infection of Salmonella enterica serovars in the mouse model.
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鼠伤寒沙门氏菌突变体衍生的带有截短脂多糖的外膜囊泡在小鼠模型中诱导针对肠道沙门氏菌血清型感染的交叉保护性免疫反应
DOI：
10.1016/j.ijmm.2016.08.004
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Kong Q
中科院分区：
文献类型：
--
作者：
Liu Q;Liu Q;Yi J;Liang K;Liu T;Roland KL;Jiang Y;Kong Q
肠道沙门氏菌引起肠道和全身性疾病，并在世界范围内受到相当大的关注。对多种血清型具有交叉保护作用的疫苗可以有效控制沙门氏菌介导的疾病。细菌衍生的外膜囊泡（OMV）具有高度免疫原性，并且能够引发保护性免疫应答。脂多糖（LPS）长度的改变可导致外膜重塑和外膜蛋白（OMP）组成的改变。在这项研究中，我们研究了截短的LPS对沙门氏菌OMV的生产和免疫原性的影响，包括OMV引起交叉保护对抗异源沙门氏菌菌株的能力。我们发现waaJ和rfbP的突变增强了囊泡形成，而waaC、waaF和waaG的突变抑制了这一过程。动物实验表明，来自waaC、rfaH和rfbP突变体的OMV与来自亲本菌株的OMV相比诱导更强的血清免疫应答，而所有突变体均引起针对野生型S.鼠伤寒攻毒。此外，用来自waaC和rfbP突变体的OMV进行鼻内或腹腔内免疫引起显著更高的交叉反应性IgG应答，并提供增强的针对S. Choleraesuis和S.肠道菌群攻击比野生型OMV。这些结果表明截短的LPS OMV能够赋予针对沙门氏菌感染的多种血清型的交叉保护。
Salmonella enterica cause diarrheal and systemic diseases and are of considerable concern worldwide. Vaccines that are cross-protective against multiple serovars could provide effective control of Salmonella-mediated diseases. Bacteria-derived outer membrane vesicles (OMVs) are highly immunogenic and are capable of eliciting protective immune responses. Alterations in lipopolysaccharide (LPS) length can result in outer membrane remodeling and composition of outer membrane proteins (OMPs) changing. In this study, we investigated the impact of truncated LPS on both the production and immunogenicity of Salmonella OMVs, including the ability of OMVs to elicit cross-protection against challenge by heterologous Salmonella strains. We found that mutations in waaJ and rfbP enhanced vesiculation, while mutations in waaC, waaF and waaG inhibited this process. Animal experiments indicated that OMVs from waaC, rfaH and rfbP mutants induced stronger serum immune responses compared to OMVs from the parent strain, while all elicited protective responses against the wild-type S. Typhimurium challenge. Furthermore, intranasal or intraperitoneal immunization with OMVs derived from the waaC and rfbP mutants elicited significantly higher cross-reactive IgG responses and provided enhanced cross-protection against S. Choleraesuis and S. Enteritidis challenge than the wild-type OMVs. These results indicate that truncated-LPS OMVs are capable of conferring cross protection against multiple serotypes of Salmonella infection.
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DOI：
10.4049/jimmunol.1100339
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kong Q;Six DA;Roland KL;Liu Q;Gu L;Reynolds CM;Wang X;Raetz CR;Curtiss R 3rd
通讯作者：
Curtiss R 3rd
影响因子：
168.9
作者：
Feasey, Nicholas A.;Dougan, Gordon;Kingsley, Robert A.;Heyderman, Robert S.;Gordon, Melita A.
通讯作者：
Gordon, Melita A.
影响因子：
6.4
作者：
Ferreira RB;Valdez Y;Coombes BK;Sad S;Gouw JW;Brown EM;Li Y;Grassl GA;Antunes LC;Gill N;Truong M;Scholz R;Reynolds LA;Krishnan L;Zafer AA;Sal-Man N;Lowden MJ;Auweter SD;Foster LJ;Finlay BB
通讯作者：
Finlay BB
影响因子：
3.2
作者：
HITCHCOCK, PJ;BROWN, TM
通讯作者：
BROWN, TM
影响因子：
3.1
作者：
Kong, Qingke;Yang, Jiseon;Curtiss, Roy, III
通讯作者：
Curtiss, Roy, III