Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment, 2016, Blank +

[rvallee]

We actually don’t know the causal pathways here. I think it’s reasonable that the pain and malaise might cause some changes in behaviour, but I wouldn’t be surprised if disease can cause changes in behaviour directly as well.

Maybe, in addition, but pain and malaise and other sickness symptoms are more than enough to explain this behaviour. For sure I have no other reason, and I've never really come across anyone saying different as far as their own experience goes.

 

[Utsikt]

I've never really come across anyone saying different as far as their own experience goes.

We probably wouldn’t be able to differentiate between them so that’s no surprise.

 

[jnmaciuch]

I haven't looked closely at that paper, I've got a headache and am struggling - but isn't that Nature paper looking at pDCs in peripheral blood only? They might be quite different when in lymph tissue or elsewhere?

We might only need the pDCs to be doing an interferon thing in PEM. So, not necessarily prolonged activation. Obviously lupus isn't ME/CFS, so things can be different.

There was a very small study somewhere that was suggesting that IRF7 is upregulated in ME/CFS - and IRF7 is part of the pDC mechanism.

The paper shows no pDCs infiltration in the skin as well in cases of cutaneous lupus. But yes you’re right that things might be slightly different in different microenvironments, or if the stimulation is only sporadic during PEM.

I was thinking along similar lines hypothesizing that TLR9 stimulation from mtDNA during muscle use or repeated neuron firing could contribute to PEM, though that would likely be involving tissue resident macrophages rather than circulating cells. The trick would be figuring out what TLR stimulus is really only present during the trigger for PEM (or at least in much higher amounts), which is what lead me to think of mtDNA.

[Edit: and, of course, thinking what other mechanism would be constantly misbehaving to produce baseline symptoms outside of PEM.]

 

[V.R.T.]

The paper shows no pDCs infiltration in the skin as well in cases of cutaneous lupus. But yes you’re right that things might be slightly different in different microenvironments, or if the stimulation is only sporadic during PEM.

I was thinking along similar lines hypothesizing that TLR9 stimulation from mtDNA during muscle use or repeated neuron firing could contribute to PEM, though that would likely be involving tissue resident macrophages rather than circulating cells. The trick would be figuring out what TLR stimulus is really only present during the trigger for PEM (or at least in much higher amounts), which is what lead me to think of mtDNA.

[Edit: and, of course, thinking what other mechanism would be constantly misbehaving to produce baseline symptoms outside of PEM.]

How goes your quest for muscle samples?

Appreciate you may not be able to divulge everything but curious to know how your work is progressing.

 

[jnmaciuch]

How goes your quest for muscle samples?

Appreciate you may not be able to divulge everything but curious to know how your work is progressing.

Slow, unfortunately, but will soon be sending out some more collaboration requests. My mentors fully support me pursuing this as a passion project but I’m obligated to prioritize the projects that are funding my PhD and my program’s academic requirements first. Which sadly has left very little time and energy left over, as I’m sure folks here can intuit.

 

[V.R.T.]

Slow, unfortunately, but will soon be sending out some more collaboration requests. My mentors fully support me pursuing this as a passion project but I’m obligated to prioritize the projects that are funding my PhD and my program’s academic requirements first. Which sadly has left very little time and energy left over, as I’m sure folks here can intuit.

Totally understandable! I remember trying to do academia with ME, it was hard going.

Hope the collaboration requests are fruitful!