Toll-like receptor 9 activation

A novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia

Styliani Goulopoulou, Takayuki Matsumoto, Gisele F. Bomfim, R. Clinton Webb

Research output: Contribution to journalArticleResearchpeer-review

58 Citations (Scopus)

Abstract

Emerging evidence suggests that in addition to being the 'power houses' of our cells, mitochondria facilitate effector responses of the immune system. Cell death and injury result in the release of mtDNA (mitochondrial DNA) that acts via TLR9 (Toll-like receptor 9), a pattern recognition receptor of the immune system which detects bacterial and viral DNA but not vertebrate DNA. The ability of mtDNA to activate TLR9 in a similar fashion to bacterial DNA stems from evolutionarily conserved similarities between bacteria and mitochondria. mtDNA may be the trigger of systemic inflammation in pathologies associated with abnormal cell death. PE (pre-eclampsia) is a hypertensive disorder of pregnancy with devastating maternal and fetal consequences. The aetiology of PE is unknown and removal of the placenta is the only effective cure. Placentas from women with PE show exaggerated necrosis of trophoblast cells, and circulating levels of mtDNA are higher in pregnancies with PE. Accordingly, we propose the hypothesis that exaggerated necrosis of trophoblast cells results in the release of mtDNA, which stimulates TLR9 to mount an immune response and to produce systemic maternal inflammation and vascular dysfunction that lead to hypertension and IUGR (intra-uterine growth restriction). The proposed hypothesis implicates mtDNA in the development of PE via activation of the immune system and may have important preventative and therapeutic implications, because circulating mtDNA may be potential markers of early detection of PE, and anti-TLR9 treatments may be promising in the management of the disease.

Original languageEnglish
Pages (from-to)429-435
Number of pages7
JournalClinical Science
Volume123
Issue number7
DOIs
StatePublished - 1 Oct 2012

Fingerprint

Toll-Like Receptor 9
Pre-Eclampsia
Mitochondrial DNA
Placenta
Blood Vessels
Immune System
Bacterial DNA
Trophoblasts
Mitochondria
Cell Death
Necrosis
Mothers
Inflammation
Pattern Recognition Receptors
Pregnancy
Viral DNA
Disease Management
Vertebrates
Pathology
Hypertension

Keywords

  • Mitochondrial DNA
  • Placenta
  • Pre-eclampsia
  • Pregnancy
  • Toll-like receptor 9
  • Vascular dysfunction

Cite this

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abstract = "Emerging evidence suggests that in addition to being the 'power houses' of our cells, mitochondria facilitate effector responses of the immune system. Cell death and injury result in the release of mtDNA (mitochondrial DNA) that acts via TLR9 (Toll-like receptor 9), a pattern recognition receptor of the immune system which detects bacterial and viral DNA but not vertebrate DNA. The ability of mtDNA to activate TLR9 in a similar fashion to bacterial DNA stems from evolutionarily conserved similarities between bacteria and mitochondria. mtDNA may be the trigger of systemic inflammation in pathologies associated with abnormal cell death. PE (pre-eclampsia) is a hypertensive disorder of pregnancy with devastating maternal and fetal consequences. The aetiology of PE is unknown and removal of the placenta is the only effective cure. Placentas from women with PE show exaggerated necrosis of trophoblast cells, and circulating levels of mtDNA are higher in pregnancies with PE. Accordingly, we propose the hypothesis that exaggerated necrosis of trophoblast cells results in the release of mtDNA, which stimulates TLR9 to mount an immune response and to produce systemic maternal inflammation and vascular dysfunction that lead to hypertension and IUGR (intra-uterine growth restriction). The proposed hypothesis implicates mtDNA in the development of PE via activation of the immune system and may have important preventative and therapeutic implications, because circulating mtDNA may be potential markers of early detection of PE, and anti-TLR9 treatments may be promising in the management of the disease.",
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Toll-like receptor 9 activation : A novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia. / Goulopoulou, Styliani; Matsumoto, Takayuki; Bomfim, Gisele F.; Webb, R. Clinton.

In: Clinical Science, Vol. 123, No. 7, 01.10.2012, p. 429-435.

Research output: Contribution to journalArticleResearchpeer-review

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