Imperial College London
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Professor David MacIntyre

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor in Reproduction Systems Medicine
 
 
 
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Contact

 

+44 (0)20 7594 2195d.macintyre Website

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rasheed:2020:10.3389/fimmu.2020.01899,
author = {Rasheed, ZBM and Lee, YS and Kim, SH and Rai, RK and Ruano, CSM and Anucha, E and Sullivan, MHF and MacIntyre, DA and Bennett, PR and Sykes, L},
doi = {10.3389/fimmu.2020.01899},
journal = {Frontiers in Immunology},
pages = {1--27},
title = {Differential response of gestational tissues to TLR3 viral priming prior to exposure to bacterial TLR2 and TLR2/6 agonists},
url = {http://dx.doi.org/10.3389/fimmu.2020.01899},
volume = {11},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Infection/inflammation is an important causal factor in spontaneous preterm birth (sPTB). Most mechanistic studies have concentrated on the role of bacteria, with limited focus on the role of viruses in sPTB. Murine studies support a potential multi-pathogen aetiology in which a double or sequential hit of both viral and bacterial pathogens leads to a higher risk preterm labour. This study aimed to determine the effect of viral priming on bacterial induced inflammation in human in vitro models of ascending and haematogenous infection.Methods: Vaginal epithelial cells, and primary amnion epithelial cells and myocytes were used to represent cell targets of ascending infection while interactions between peripheral blood mononuclear cells (PBMCs) and placental explants were used to model systemic infection. To model the effect of viral priming upon the subsequent response to bacterial stimuli, each cell type was stimulated first with a TLR3 viral agonist, and then with either a TLR2 or TLR2/6 agonist, and responses compared to those of each agonist alone. Immunoblotting was used to detect cellular NF-κB, AP-1, and IRF-3 activation. Cellular TLR3, TLR2, and TLR6 mRNA was quantified by RT-qPCR. Immunoassays were used to measure supernatant cytokine, chemokine and PGE2 concentrations.Results: TLR3 (“viral”) priming prior to TLR2/6 agonist (“bacterial”) exposure augmented the pro-inflammatory, pro-labour response in VECs, AECs, myocytes and PBMCs when compared to the effects of agonists alone. In contrast, enhanced anti-inflammatory cytokine production (IL-10) was observed in placental explants. Culturing placental explants in conditioned media derived from PBMCs primed with a TLR3 agonist enhanced TLR2/6 agonist stimulated production of IL-6 and IL-8, suggesting a differential response by the placenta to systemic inflammation compared to direct infection as a result of haematogenous spread. TLR3 agonism generally caused increased m
AU  - Rasheed,ZBM
AU  - Lee,YS
AU  - Kim,SH
AU  - Rai,RK
AU  - Ruano,CSM
AU  - Anucha,E
AU  - Sullivan,MHF
AU  - MacIntyre,DA
AU  - Bennett,PR
AU  - Sykes,L
DO  - 10.3389/fimmu.2020.01899
EP  - 27
PY  - 2020///
SN  - 1664-3224
SP  - 1
TI  - Differential response of gestational tissues to TLR3 viral priming prior to exposure to bacterial TLR2 and TLR2/6 agonists
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2020.01899
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2020.01899/full
UR  - http://hdl.handle.net/10044/1/82390
VL  - 11
ER  -
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