Neutrophil swarming and extracellular trap formation play a significant role in Alum adjuvant activity.
Neutrophil swarming and extracellular trap formation play a significant role in Alum adjuvant activity.
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DOI：
10.1038/s41541-016-0001-5
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发表时间：
2017
期刊：
影响因子：
9.2
通讯作者：
Brewer JM
中科院分区：
文献类型：
--
作者：
Stephen J;Scales HE;Benson RA;Erben D;Garside P;Brewer JM
每年有超过60亿剂疫苗接种，其中大多数含有铝基佐剂，但我们仍然没有完全了解它们的作用机制。最近的证据已经确定宿主DNA和下游传感在铝佐剂（氢氧化铝）活性中起重要作用。然而，这种DNA的细胞来源，它如何被免疫系统感知，以及它对疫苗接种的影响仍不清楚。在这里，我们表明，非常早期的注射部位反应的特点是炎症趋化因子的生产和中性粒细胞招聘。活体成像显示明矾注射部位是中性粒细胞群和细胞外DNA链的焦点。这些链被证实为中性粒细胞胞外陷阱，由于其对DNA酶的敏感性和缺乏肽基精氨酸脱亚胺酶4的小鼠。在PAD 4 −/−小鼠中的进一步研究证实了中性粒细胞胞外陷阱形成在明矾的佐剂活性中的重要作用。通过揭示招募到明矾注射部位的中性粒细胞作为免疫系统检测到的DNA的来源，这项研究提供了明矾注射和增强佐剂活性的DNA传感器激活之间缺失的环节，阐明了这种重要疫苗成分的关键作用机制。研究人员已经确定了氢氧化铝（明矾）提高联合接种疫苗效力的作用机制。在这项研究中，来自英国格拉斯哥大学的James Brewer及其同事研究了明矾联合给药在小鼠模型中的作用，发现该化合物诱导称为中性粒细胞的免疫细胞聚集在免疫部位周围并产生中性粒细胞胞外陷阱（NET）。NET，在中性粒细胞死亡的某些条件下形成的DNA和细胞内容物的网络，消灭病原体并促进其消除。这项研究建立在以前的研究基础上，证明明矾人工刺激这一途径，以增强对疫苗抗原的适应性免疫反应，增加其免疫原性。作者还建议进一步研究中性粒细胞成分作为潜在的治疗药物。
There are over 6 billion vaccine doses administered each year, most containing aluminium-based adjuvants, yet we still do not have a complete understanding of their mechanisms of action. Recent evidence has identified host DNA and downstream sensing as playing a significant role in aluminium adjuvant (aluminium hydroxide) activity. However, the cellular source of this DNA, how it is sensed by the immune system and the consequences of this for vaccination remains unclear. Here we show that the very early injection site reaction is characterised by inflammatory chemokine production and neutrophil recruitment. Intravital imaging demonstrates that the Alum injection site is a focus of neutrophil swarms and extracellular DNA strands. These strands were confirmed as neutrophil extracellular traps due to their sensitivity to DNAse and absence in mice deficient in peptidylarginine deiminase 4. Further studies in PAD4−/− mice confirmed a significant role for neutrophil extracellular trap formation in the adjuvant activity of Alum. By revealing neutrophils recruited to the site of Alum injection as a source of the DNA that is detected by the immune system this study provides the missing link between Alum injection and the activation of DNA sensors that enhance adjuvant activity, elucidating a key mechanism of action for this important vaccine component. Researchers have identified the mechanism of action in which aluminium hydroxide (alum) boosts the efficacy of co-administered vaccines. In this study, James Brewer and colleagues from the University of Glasgow, UK, studied the effects of alum co-administration in a mouse model, finding that the compound induces immune cells, called neutrophils, to swarm around the site of immunization and produce neutrophil extracellular traps (NETs). NETs, webs of DNA and cell contents formed under certain conditions of neutrophil cell death, immobilize pathogens and promote their elimination. This study builds on previous research and demonstrates that alum artificially stimulates this pathway to boost the adaptive immune response to vaccine antigens, increasing their immunogenicity. The authors also suggest further study into neutrophil components as potential therapeutic agents.
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影响因子：
3.7
作者：
Hemmers S;Teijaro JR;Arandjelovic S;Mowen KA
通讯作者：
Mowen KA
DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
DOI：
10.4049/jimmunol.0900164
发表时间：
2009-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
McKee AS;Munks MW;MacLeod MK;Fleenor CJ;Van Rooijen N;Kappler JW;Marrack P
通讯作者：
Marrack P
影响因子：
4.4
作者：
Li, Hanfen;Willingham, Stephen B.;Ting, Jenny P. -Y.;Re, Fabio
通讯作者：
Re, Fabio
影响因子：
56.9
作者：
Garside, P;Ingulli, E;Jenkins, MK
通讯作者：
Jenkins, MK