The complosome is a newly-discovered intracellular part of the complement system. Could it play a role in ME/CFS?

[Hip]

ME/CFS involves persistent intracellular viral infections, which the immune system does not seem to be able to clear.

So logically, it's possible that there might be some defect or weakness in the intracellular immune response in ME/CFS patients, that prevents the immune system from eliminating intracellular viruses. We normally think of interferon in the context of intracellular infections, as interferon activates intracellular immunity.

However, I just came across another aspect of intracellular immunity, which was only discovered about a decade ago, namely the complosome, which is the intracellular counterpart of the complement system, and plays a role in defending against viral infection.

If there were a weakness or dysfunction in the complosome, this might explain why ME/CFS patients cannot clear their intracellular viral infections. Interestingly enough, the complosome also controls mitochondrial activity and glycolysis, so a dysfunctional complosome might in addition cause the energy deficits found in ME/CFS.



Since research into the complosome is still in its infancy, there is not much known about how to boost or inhibit this intracellular complement system. I was hoping to find some drug or compound which might boost the ability of the complosome to clear intracellular viral infections, but could not find anything.

But here is some general information about the complosome:

In 2013, a study on complement subverted our perception of complement activation and showed that complement is not confined to the extracellular space but can also occur intracellularly. This landmark study discovered that the intracellular reserves of C3, C3aR, and cathepsin L are present in human CD4 cells

Furthermore, the intracellular C3 stores and 'Tonic' intracellular C3a generation have also been shown to occur in monocytes, neutrophils, CD8 cells, B-cells, epithelial cells, endothelial cells, and fibroblasts, implying that intracellular complement activation might be of broad physiological significance.

The complosome has been shown to play a critical function in regulating T cell responses, cell physiology (such as metabolism), inflammatory disease processes, and cancer

Source: The role of the complosome in health and disease

The complosome controls mitochondrial activity, glycolysis, oxidative phosphorylation, cell survival and gene regulation in innate and adaptive immune cells, and in non-immune cells, such as fibroblasts and endothelial and epithelial cells.

Perturbations in complosome activities contribute to human disease, including infections and infection-related pathological conditions, arthritic disease, atherosclerosis, cancer and kidney disease.

Lysosomes and mitochondria, which are key components of cellular metabolic machinery, are hotspots of complosome activity. For example, in several cell populations, the lysosome contains stores of C3.

Reductions in cell-autonomous C3 and/or C5 generation, or CD46 expression in human CD4 and CD8 T cells are associated with failure to induce protective TH1 cell and CTL responses, respectively.

So this is saying low levels of intracellular complosome C3 results in insufficient antiviral Th1 responses; it's often been theorised that ME/CFS patients cannot clear their viral infections because of weak Th1 immunity; thus boosting intracellular C3 might restore the antiviral Th1 response.

Targeting upstream inducers of complosome expression and activity is another emerging strategy. For example, cholesterol crystals are known complosome activators.

Type I interferons control C3 expression during viral infections

The integrin lymphocyte function-associated antigen 1 has been identified as a master regulator of C3 expression in immune cells and might therefore also warrant consideration as a cell-surface target for intracellular C3 control.

Source: Complosome — the intracellular complement system

 

[Hip]

@datadragon, nothing in your post seems to have any relevance to the complosome. Please keep on topic.