Imperial College London

Dr John S Tregoning

Faculty of MedicineDepartment of Infectious Disease

Professor in Vaccine Immunology
 
 
 
//

Contact

 

john.tregoning Website

 
 
//

Location

 

456 (Shattock Group)Wright Fleming WingSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@unpublished{Mooney:2019:10.1101/846626,
author = {Mooney, JP and Qendro, T and Keith, M and Philbey, AW and Groves, HT and Tregoning, JS and Goodier, MR and Riley, EM},
doi = {10.1101/846626},
publisher = {bioRxiv},
title = {Natural Killer cells dampen the pathogenic features of recall responses to influenza infection},
url = {http://dx.doi.org/10.1101/846626},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - UNPB
AB - Despite evidence of augmented Natural Killer (NK) cell responses after influenza vaccination, the role of these cells in vaccine-induced immunity remains unclear. Here, we hypothesized that NK cells might increase viral clearance but possibly at the expense of increased severity of pathology. On the contrary, we found that NK cells serve a homeostatic role during influenza virus infection of vaccinated mice, allowing viral clearance with minimal pathology. Using a diphtheria toxin receptor transgenic mouse model, we were able to specifically deplete NKp46+ NK cells through the administration of diphtheria toxin. Using this model, we assessed the effect of NK cell depletion prior to influenza challenge in vaccinated and unvaccinated mice. NK-depleted, vaccinated animals lost significantly more weight after viral challenge than vaccinated NK intact animals, indicating that NK cells ameliorate disease in vaccinated animals. However, there was also a significant reduction in viral load in NK-depleted, unvaccinated animals indicating that NK cells also constrain viral clearance. Depletion of NK cells after vaccination, but 21 days before infection, did not affect viral clearance or weight loss - indicating that it is the presence of NK cells during the infection itself that promotes homeostasis. Further work is needed to identify the mechanism(s) by which NK cells regulate adaptive immunity in influenza-vaccinated animals to allow efficient and effective virus control whilst simultaneously minimizing inflammation and pathology.
AU - Mooney,JP
AU - Qendro,T
AU - Keith,M
AU - Philbey,AW
AU - Groves,HT
AU - Tregoning,JS
AU - Goodier,MR
AU - Riley,EM
DO - 10.1101/846626
PB - bioRxiv
PY - 2019///
TI - Natural Killer cells dampen the pathogenic features of recall responses to influenza infection
UR - http://dx.doi.org/10.1101/846626
UR - https://www.biorxiv.org/content/10.1101/846626v1
ER -