Detection of prokaryotic mRNA signifies microbial viability and promotes immunity.
Detection of prokaryotic mRNA signifies microbial viability and promotes immunity.
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DOI：
10.1038/nature10072
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发表时间：
2011-05-22
期刊：
影响因子：
64.8
通讯作者：
Blander, J. Magarian
中科院分区：
文献类型：
--
作者：
Sander, Leif E.;Davis, Michael J.;Boekschoten, Mark V.;Amsen, Derk;Dascher, Christopher C.;Ryffel, Bernard;Swanson, Joel A.;Mueller, Michael;Blander, J. Magarian
人们早就知道活疫苗比灭活疫苗能引发更强烈的免疫反应。这归因于活微生物复制和表达专门的毒力因子的能力，这些毒力因子促进了其宿主的入侵和感染。然而，保护性免疫通常可以通过单次注射去除毒力因子的活而非死的减毒微生物来实现。用于提醒免疫系统的病原体相关分子模式（Pathogen associated molecular patterns, PAMPs）存在于活疫苗和灭活疫苗中，这表明活微生物未被纳入灭活疫苗的某些特征不明确的方面在诱导保护性免疫方面特别有效。本研究表明，先天免疫系统可以通过检测一类特殊的与生存能力相关的PAMPs（维生素-PAMPs）直接感知微生物的生存能力。我们将原核信使RNA （mRNA）鉴定为仅存在于活菌中的vita-PAMP，对其的识别引发独特的先天反应和强大的适应性抗体反应。值得注意的是，迄今为止，由活力和原核mRNA引起的先天反应被认为是为致病菌保留的，但我们表明，即使是无菌组织中的非致病菌，只要它们活着，也可以引发类似的反应。因此，免疫系统通过搜寻PAMPs来寻找微生物生命和感染性的特征，从而积极地评估感染风险。检测到维生素- pamps会触发一种对死细菌没有保证的警报模式。因此，含有维生素- pamps的疫苗配方可以将活疫苗的优越保护与死疫苗的安全性结合起来。
Live vaccines have long been known to trigger far more vigorous immune responses than their killed counterparts. This has been attributed to the ability of live microorganisms to replicate and express specialized virulence factors that facilitate invasion and infection of their hosts. However, protective immunization can often be achieved with a single injection of live, but not dead, attenuated microorganisms stripped of their virulence factors. Pathogen associated molecular patterns (PAMPs), which serve to alert the immune system, are present in both live and killed vaccines, suggesting that certain poorly characterized aspects of live microorganisms, not incorporated in dead vaccines, are particularly effective at inducing protective immunity. Here we show that the innate immune system can directly sense microbial viability through detection of a special class of viability-associated PAMPs (vita-PAMPs). We identify prokaryotic messenger RNA (mRNA) as a vita-PAMP present only in viable bacteria, recognition of which elicits a unique innate response and a robust adaptive antibody response. Notably, the innate response evoked by viability and prokaryotic mRNA was thus far considered to be reserved for pathogenic bacteria, but we show that even nonpathogenic bacteria in sterile tissues can trigger similar responses, provided they are alive. Thus, the immune system actively gauges the infectious risk by scouring PAMPs for signatures of microbial life and thus infectivity. Detection of vita-PAMPs triggers an alert mode not warranted for dead bacteria. Vaccine formulations that incorporate vita-PAMPs could thus combine the superior protection of live vaccines with the safety of dead vaccines.
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影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
3.1
作者：
MAURELLI, AT;BAUDRY, B;SANSONETTI, PJ
通讯作者：
SANSONETTI, PJ
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
82.9
作者：
Brockstedt, DG;Bahjat, KS;Dubensky, TW
通讯作者：
Dubensky, TW
影响因子：
56.9
作者：
BUCHMEIER, NA;HEFFRON, F
通讯作者：
HEFFRON, F