Disease Tolerance versus Resistance

Disease tolerance and disease resistance are various ways to confer immunity. At the beginning of an infection, when nutrients are plentiful, sacrificing cell survival to kill the infecting microbe can be acceptable since nutrition may be adequate to bring about tissue replacement. This damage has, as a consequence, tissue and immune cell aging due to continuous replacement of cells by others, many times over. As nutrients dwindle, in the face of increased cellular and microbe activitites and toxic outputs, this strategy may fail to yield the desired outcome

Low methionine, the principal participant in the increased lifespan following dietary restriction, becomes evident as the methionine salvage pathway comes in to recycle methionine from spermine, spermidine and putrescine(polyamines). APIP is an enzyme that makes MTA that eventually provides methionine but at the same time prevents cell death, as if by monitoring this nutrient availability. The disease becomes less debilitating, in spite of the microbial load. Inflammation becomes less evident. Repair is more prominent. This is usually a less infectious, carrier state which may resolve later as the necessary nutrients are replenished. Pyroptosis and apoptosis(programmed cell deaths known to help clear infections fast but equally promote spread) may then return. Therefore, microbes should be killed preferably at the beginning and at the end. In-between, tolerance should be sought, as the microbes are not multiplying but are dying from the effects of their own toxins and nutritional deprivation, anyway. And that is what happens with persistent intracellular(tolerated) infectious microbes that get reactivated with time, due to nutritional stress (starvation, not fasting), over-nutrition and psychological stress, to come out and form biofilm. Most microbes will not want to kill the host cell in which they reside but rather develop strategies to inactivate and prevent it from mounting any defense. Reactivation of the infected immune cell will succeed in making the cell undergo inflammatory programmed cell death that sends a distress signal to other immune cells to come and clear the microbe and prevent further spread.

Dr Oliver Verbe Birnso M.D.

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