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Activation of a TLR9 mediated innate immune response in preeclampsia.
Williamson, Rachel D McCarthy, Fergus P Kenny, Louise C McCarthy, Cathal M
Williamson, Rachel D
McCarthy, Fergus P
Kenny, Louise C
McCarthy, Cathal M
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Date
2019-04-11
Date Submitted
Keywords
PRE-ECLAMPSIA
IMMUNE SYSTEM
PREGNANCY
IMMUNE SYSTEM
PREGNANCY
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Start Date
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Abstract
Preeclampsia is a multisystemic disorder leading to the development of a placental ischemic
microenvironment with a resultant increase in oxidative stress. There is evidence that mitochondrial
dysfunction and the innate immune system both play a role in the pathophysiology of this disease.
Mitochondrial DAMPs such as mtDNA bind specifc pattern recognition receptors such as Toll-like
receptor 9 (TLR9) on the endosomal surface of immune cells, in particular neutrophils, subsequently
activating them and triggering an innate response. We hypothesised that the exaggerated innate
immune response seen in preeclampsia is provoked by dysfunctional mitochondria. Here we provide
evidence that TLR9 activity is signifcantly increased at time of disease in women with preeclampsia.
Furthermore, we show activation of neutrophil markers, Calprotectin, Myeloperoxidase (MPO), and IL-8
are signifcantly increased at time of disease compared to uncomplicated pregnancies. This research
supports a potential role of TLR9 activation of an innate immune response evident in preeclampsia
which may possibly be initially triggered by dysfunctional mitochondria.
Language
en
Citation
ISSN
2045-2322
eISSN
ISBN
DOI
10.1038/s41598-019-42551-w
PMID
30976066
PMCID
Sponsorships
C. McCarthy and L.C. Kenny are supported by a Science FoundationIreland (SFI) Program Grant for INFANT
(12/RC/2272) and HealthResearch Board Ireland, Health Research Award (HRA-POR-2015-1240) for fnancial
support