I should point out that Jonathan Edwards uncovered something of a
potential flaw in Michael VanElzakker's vagus nerve infection theory of ME/CFS, which is as follows:
It is the
satellite glial cells in the vagus nerve that Michael VanElzakker proposes may be chronically infected in ME/CFS patients. Like any infected cell, these infected satellite glial cells will be secreting inflammatory cytokines to signal they are infected.
The vagus nerve has receptors for such inflammatory cytokines: the vagus has IL-1β receptors, and I think also TNF-α receptors, to detect these cytokines released from infections. The vagus is an infection detector. When the vagus detects these cytokines from infections, it then signals to the brain to switch on sickness behavior (which manifests many of the symptoms of ME/CFS).
However — and here is the problem spotted by Jonathan Edwards — these vagus nerve IL-1β and TNF-α receptors are found at the far end of the dendrite of a vagus sensory neuron, and this position is several centimeters away from the cell body of the sensory neuron, where the satellite glial cells are located.
So there is a distance of several centimeters between the infection and the infection-detecting IL-1β and TNF-α receptors.
Now secreted IL-1β and TNF-α only have a short range, so any IL-1β or TNF-α released from infected satellite glial cells would likely not reach, in any great concentration, these IL-1β and TNF-α receptors located several centimeters away.
This means a satellite glial cell infection in the vagus nerve would probably not be activating the IL-1β and TNF-α receptors to any great degree, and thus this infection may not be able to induce sickness behavior in the way Michael VanElzakker proposes.
See
this post, and the prior and subsequent discussion in that thread for more details of this possible flaw.
I did suggest in that post that perhaps the
Schwann cells of the vagus might be chronically infected, rather than the satellite glial cells. Schwann cells are found in closer proximity to the IL-1β and TNF-α receptors. However, Schwann cell infections appear to be very rare. So whether this idea can rescue the vagus nerve infection theory, I am not sure. Certainly though Schwann cells possess both the CAR and DAF receptors which coxsackievirus B uses to enter and infect cells (see
this post).
However, there is another possibility that may keep Michael VanElzakker's very intriguing vagus nerve / sickness behavior theory of ME/CFS alive: I suggested that the vagus itself may not be chronically infected, but rather the cells the vagus connects to may be infected.
And indeed, we know this is the case, as the
parietal cells in the stomach, which the efferent vagus directly connects to (and thereby controls their release of stomach acid), have been shown to be chronically infected in 82% of ME/CFS patients (by Dr Chia in his
2007 study). So the vagus is in close proximity to these chronically infected parietal cells.
Thus provided that the vagus IL-1β and TNF-α receptors themselves are in sufficiently close proximity to these parietal cells, these receptors may be getting persistently activated by the inflammatory cytokines secreted by the infected parietal cells, thus causing the vagus to signal to the brain to switch on sickness behavior.
However, I am not sure just how close the vagus IL-1β and TNF-α receptors are to the parietal cells that the efferent vagus innervates. To answer this question would require in-depth knowledge of vagus anatomy. Perhaps
@Jonathan Edwards might know.
By the way, I came across
this interesting study by Patricio T Huerta that actually measured the electrical signals send along the afferent vagus nerve to the brain when the nerve is activated by IL-1β or TNF-α.
