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Toll-Like Receptor 3 Activation During Preg.

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Toll-Like Receptor 3 Activation During Preg.

Postby caryn » Fri Oct 02, 2009 07:45 pm

by caryn (10111 Posts), Fri Oct 02, 2009 07:45 pm

These findings demonstrate that sustained maternal immune system activation via TLR3 during pregnancy causes PE-like symptoms in rats and suggest that viral infection during pregnancy may contribute to the development of PE.

http://www.ncbi.nlm.nih.gov/pubmed/19779466

Catherine works on this stuff. I think basically it's saying that anything that pisses off your immune system in pregnancy pisses off your immune system, and can therefore lead to preeclampsia, which is pretty much *defined* at this point as an ineluctably pissed-off immune system in pregnancy.

Hopefully Catherine will riff on this further. :-)

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Re : Toll-Like Receptor 3 Activation During Preg.

Postby catherine » Fri Oct 02, 2009 09:32 pm

by catherine (2832 Posts), Fri Oct 02, 2009 09:32 pm

Uh... yes I do, in a somewhat peripheral sense.

Um, the disconnect for me here is that TLR3 specifically recognizes double stranded RNA which only occurs in nature in the context of certain (but not all) viruses. The poly I:C administered to the animals in these experiments is a synthetic compound that mimics viral RNA. So immune cells that carry this receptor become activated when the viral ligand sticks to it. Hence the authors' comment that viral infection during pregnancy could trigger preeclampsia.

I'd have thought that someone somewhere has looked quite exhaustively by now for some evidence for an infectious cause or trigger for preeclampsia.....
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Re : Toll-Like Receptor 3 Activation During Preg.

Postby blythe » Sat Oct 03, 2009 03:28 pm

by blythe (3060 Posts), Sat Oct 03, 2009 03:28 pm

I did a quick pubmed search - looks like there's a (small?) correlation, and this current study is looking at possible causal relationships?

http://www.ncbi.nlm.nih.gov/pubmed/18166297
Maternal infection and risk of preeclampsia: systematic review and metaanalysis.
...Urinary tract infection and periodontal disease during pregnancy are associated with an increased risk of preeclampsia. More studies are required to verify this as well as to explore whether or not such relationships are causal and, if so, the mechanisms involved.

http://www.ncbi.nlm.nih.gov/pubmed/17577649
Association between maternal infections and preeclampsia: a systematic review of epidemiologic studies.
CONCLUSIONS: In our analysis, any infection (bacterial or viral) was associated with a two-fold higher risk of preeclampsia. This association may provide a potential explanation for preeclampsia-related inflammation.
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Re : Toll-Like Receptor 3 Activation During Preg.

Postby jgrumet » Sat Oct 03, 2009 11:40 pm

by jgrumet (520 Posts), Sat Oct 03, 2009 11:40 pm

I always thought that even at implantation you have PE, but it doesn't show up until later...is that wrong?

What kind of a viral infection are they talking about? I know a lot of women said they had a bad illness with their PE pregnancy (such as swine flu), could that possibly be the trigger?
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Re : Toll-Like Receptor 3 Activation During Preg.

Postby my3tatertots » Fri Oct 23, 2009 05:25 pm

by my3tatertots (78 Posts), Fri Oct 23, 2009 05:25 pm

That's interesting. I've had PIH/PE twice now but in my second pregnancy I developed it much earlier - 32 weeks vs 40 weeks. I also had a viral infection at 20 weeks with my second pregnancy that was dx'd and treated by my OB. I wonder if the strain on my immune system caused PE to show up earlier. Of course there was at least 10 weeks in between my viral infection and the start of PE so who knows.
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Re : Toll-Like Receptor 3 Activation During Preg.

Postby lisainnj » Wed Oct 28, 2009 07:57 pm

by lisainnj (595 Posts), Wed Oct 28, 2009 07:57 pm

When I lost Francesca, the hospital had a cluster of three of us with preeclampsia at 20 weeks, one about ten days before and one a day or two later than me.

I was hit with one upper respiratory infection after another in that pregnancy, viral, bacterial sinus, viral - felt constantly sick and inflamed. Sucks that a little thing like that can contribute.
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Re : Toll-Like Receptor 3 Activation During Preg.

Postby bmitchell » Sat Feb 06, 2010 02:48 am

by bmitchell (1 Posts), Sat Feb 06, 2010 02:48 am

As the senior author of the paper ya'll you are discussing first off I am honored that Caryn and others have commented on our work and findings-this certainly makes a basic scientist feel good that our work may have some real life implications. Secondly, hopefully to clarify, we were able to induce PE-like symptoms in rats by excessively activating the mom's immune system during pregnancy. As Caryn mentioned in somewhat other terms, the mom's immune system is already activated trying to prepare for and accept a half-foreign fetus. This represents a pro-inflammatory state in preparation for these events. What we showed that is that the events associated with pregnancy do not cause PE alone, nor does immune system activation in non-pregnant animals, but the combination of the 2 caused PE like symptoms in animals. Toll-like receptor 3 senses double-stranded RNA (which are rotavirus and rheovirus), but several other factors can activate these receptors during pregnancy. While I would love to prove that every case of PE is caused by previous exposure to rheo/rotavirus, necrotic (dying) cells can also activate TLR3 and other viruses (single stranded RNA viruses such as CMV, HPV, etc. when they divide create double-stranded RNA) can also activate TLR3. We are presently determining whether a mom has to have an active viral infection vs. a latent one as well as whether TLR3 is activated in women with PE vs. normotensive pregnant women. My ultimate goal, if we find that TLR3 is activated in PE women, is to design TLR3 inhibitors as a therapy to prevent PE after it is diagnosed. In support, we have developed a mouse model of the disease, somewhat similar to the rat model in the paper, but we are able to gather a substantial amount more data regarding the possible mechanisms and are now able to test various therapeutics. While it is no consolation to those of you who have experienced PE, hopefully we can treat this in women in the near future.
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Re : Toll-Like Receptor 3 Activation During Preg.

Postby l412angel » Sat Feb 06, 2010 10:13 am

by l412angel (1746 Posts), Sat Feb 06, 2010 10:13 am

I as well had a respratory infection with Cara about a month before I delivered her...hmmm interesting!
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Re : Toll-Like Receptor 3 Activation During Preg.

Postby emmie160 » Sat Feb 06, 2010 11:33 am

by emmie160 (11 Posts), Sat Feb 06, 2010 11:33 am

This is so interesting!!

Three weeks before I was diagnosed I had suspected swine flu. I never felt 'right' after. I long suspected that the flu had triggered off my hellp/pe but my doc said otherwise and thought that my pe only started a few days before I was diagnosed. I, however am convinced the flu set off my syptoms.

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Re : Toll-Like Receptor 3 Activation During Preg.

Postby caryn » Sun Feb 14, 2010 06:38 pm

by caryn (10111 Posts), Sun Feb 14, 2010 06:38 pm

I don't know how I missed this when you posted, Brett, but thank you for dropping by to clarify!

So this ties into the question about whether the soluble FLT produced by the placenta in response to the placental hypoxia is a chicken, or an egg, then, right? It certainly makes a bunch of necrotic cells... but so does initial implantation.
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