NFkappaB, apoptosis, and cytotoxic microbes

[Guest guest]

Since apoptosis of infected macrophages is beneficial to clearance of

M. tuberculosis and likely other pathogens which persist in the

phagocyte, I had often wondered why immune activation of a leucocyte

via NFkappaB makes apoptosis significantly more difficult.

Entameba histolyica can induce apoptosis in any cell other than an

*activated* leucocyte, by an unclear mechanism. If NFkB signaling did

not oppose apoptosis, no cell would be able to combat E. histolytica,

and it would proliferate massively and destroy the entire body.

Yersinia pestis, the black death, is also cytotoxic via apoptosis,

and at least some people are saying that inhibition of NFkB signaling

is key to the action of the relevant toxin. I'm not sure activated

phagocytes become more refractory to the Yersinia toxins but I would

assume so. It would be interesting to know whether TB hit Europe

harder in the aftermath of selection by the extremely destructive

black plague, which ravaged basically all of europe. Humans with more

robust anti-apoptosis signaling coupled to NFkB may have been

likelier to survive the black death, and they might then give rise to

a TB-suceptible population.

If every phagocyte in the vicinity of a microbial intruder dies,

obviously you might as well just not have phagocytes. You wouldnt

stand a chance in hell. Therefore, in the context of infection the

body has to secure proper control of the apoptosis signaling in

activated phagocytes at any cost whatsoever, and we may pay a price

for certain coarsities of the process of that protection.

If the set of important pathogens faced by humans is distinctive

because of our social behavior and close contact with domestic and

pest animals (the black death was supposedly vectored by rat fleas),

it is also interesting to wonder if that might have any effect on how

human immunity operates. This would only occur if the set of

pathogens whose success in us depends on our unique behavior has, on

average, distinct charecteristics compared to other pathogens.