Stephen, J., Scales, H.E. , Benson, R.A. , Erben, D., Garside, P. and Brewer, J.M. (2017) Neutrophil swarming and extracellular trap formation play a significant role in Alum adjuvant activity. npj Vaccines, 2, 1. (doi: 10.1038/s41541-016-0001-5) (PMID:29263862) (PMCID:PMC5604741)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Brewer, Professor James and Garside, Professor Paul and Erben, Mr Dan and Benson, Dr Robert and Stephen, Dr Jillian and Scales, Dr Hannah |
| Authors: | Stephen, J., Scales, H.E., Benson, R.A., Erben, D., Garside, P., and Brewer, J.M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | npj Vaccines |
| Publisher: | Nature Publishing Group |
| ISSN: | 2059-0105 |
| ISSN (Online): | 2059-0105 |
| Published Online: | 23 January 2017 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in npj Vaccines 2:1 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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